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111 results on '"Trojani A."'

1. Braided Scalar Quantum Electrodynamics

Author

Ćirić, Marija Dimitrijević, Nikolić, Biljana, Radovanović, Voja, Szabo, Richard J., Trojani, Guillaume, Ćirić, Marija Dimitrijević, Nikolić, Biljana, Radovanović, Voja, Szabo, Richard J., and Trojani, Guillaume

Abstract

We formulate scalar electrodynamics in the braided $L_\infty$-algebra formalism and study its perturbative expansion in the algebraic framework of Batalin-Vilkovisky quantization. We confirm that UV/IR mixing is absent at one-loop order in this noncommutative field theory, and that the non-anomalous Ward-Takahashi identities for the braided gauge symmetry are satisfied., Comment: 48 pages

Published
2024

2. Braided scalar quantum field theory

Author

Bogdanović, Djordje, Ćirić, Marija Dimitrijević, Radovanović, Voja, Szabo, Richard J., Trojani, Guillaume, Bogdanović, Djordje, Ćirić, Marija Dimitrijević, Radovanović, Voja, Szabo, Richard J., and Trojani, Guillaume

Abstract

We formulate scalar field theories in a curved braided $L_\infty$-algebra formalism and analyse their correlation functions using Batalin-Vilkovisky quantization. We perform detailed calculations in cubic braided scalar field theory up to two-loop order and three-point multiplicity. The divergent tadpole contributions are eliminated by a suitable choice of central curvature for the $L_\infty$-structure, and we confirm the absence of UV/IR mixing. The calculations of higher loop and higher multiplicity correlators in homological perturbation theory are facilitated by the introduction of a novel diagrammatic calculus. We derive an algebraic version of the Schwinger-Dyson equations based on the homological perturbation lemma, and use them to prove the braided Wick theorem., Comment: 41 pages; v2: typos corrected; v3: minor changes and typos fixed

Published
2024

3. Occurrence of L1M Elements in Chromosomal Rearrangements Associated to Chronic Myeloid Leukemia (CML): Insights from Patient-Specific Breakpoints Characterization

Author

L’Abbate, A, Moretti, V, Pungolino, E, Micheloni, G, Valli, R, Frattini, A, Barcella, M, Acquati, F, A Reinbold, R, Costantino, L, Ferrara, F, Trojani, A, Ventura, M, Porta, G, Cairoli, R, Alberto L’Abbate, Vittoria Moretti, Ester Pungolino, Giovanni Micheloni, Roberto Valli, Annalisa Frattini, Matteo Barcella, Francesco Acquati, Rolland A Reinbold, Lucy Costantino, Fulvio Ferrara, Alessandra Trojani, Mario Ventura, Giovanni Porta, Roberto Cairoli, L’Abbate, A, Moretti, V, Pungolino, E, Micheloni, G, Valli, R, Frattini, A, Barcella, M, Acquati, F, A Reinbold, R, Costantino, L, Ferrara, F, Trojani, A, Ventura, M, Porta, G, Cairoli, R, Alberto L’Abbate, Vittoria Moretti, Ester Pungolino, Giovanni Micheloni, Roberto Valli, Annalisa Frattini, Matteo Barcella, Francesco Acquati, Rolland A Reinbold, Lucy Costantino, Fulvio Ferrara, Alessandra Trojani, Mario Ventura, Giovanni Porta, and Roberto Cairoli

Abstract

Chronic myeloid leukemia (CML) is a rare myeloproliferative disorder caused by the reciprocal translocation t(9;22)(q34;q11) in hematopoietic stem cells (HSCs). This chromosomal translocation results in the formation of an extra-short chromosome 22, called a Philadelphia chromosome (Ph), containing the BCR-ABL1 fusion gene responsible for the expression of a constitutively active tyrosine kinase that causes uncontrolled growth and replication of leukemic cells. Mechanisms behind the formation of this chromosomal rearrangement are not well known, even if, as observed in tumors, repetitive DNA may be involved as core elements in chromosomal rearrangements. We have participated in the explorative investigations of the PhilosoPhi34 study to evaluate residual Ph+ cells in patients with negative FISH analysis on CD34+/lin- cells with gDNA qPCR. Using targeted next-generation deep sequencing strategies, we analyzed the genomic region around the t(9;22) translocations of 82 CML patients and one CML cell line and assessed the relevance of interspersed repeat elements at breakpoints (BP). We found a statistically higher presence of LINE elements, in particular belonging to the subfamily L1M, in BP cluster regions of both chromosome 22 and 9 compared to the whole human genome. These data suggest that L1M elements could be potential drivers of t(9;22) translocation leading to the generation of the BCR-ABL1 chimeric gene and the expression of the active BCR-ABL1-controlled tyrosine kinase chimeric protein responsible for CML.

Published
2023

4. Mutational Landscape of Bone Marrow CD19 and CD138 Cells in Waldenström Macroglobulinemia (WM) and IgM Monoclonal Gammopathy of Undetermined Significance (IgM MGUS)

Author

Trojani, A, Beghini, A, Bossi, L, Stefanucci, M, Palumbo, C, Greco, A, Frustaci, A, Di Camillo, B, Montillo, M, Cairoli, R, Trojani, Alessandra, Beghini, Alessandro, Bossi, Luca Emanuele Emanuele, Stefanucci, Marta Rachele, Palumbo, Cassandra, Greco, Antonino, Frustaci, Annamaria, Di Camillo, Barbara, Montillo, Marco, Cairoli, Roberto, Trojani, A, Beghini, A, Bossi, L, Stefanucci, M, Palumbo, C, Greco, A, Frustaci, A, Di Camillo, B, Montillo, M, Cairoli, R, Trojani, Alessandra, Beghini, Alessandro, Bossi, Luca Emanuele Emanuele, Stefanucci, Marta Rachele, Palumbo, Cassandra, Greco, Antonino, Frustaci, Annamaria, Di Camillo, Barbara, Montillo, Marco, and Cairoli, Roberto

Published
2023

5. A Nine-Gene Expression Signature Distinguished a Patient with Chronic Lymphocytic Leukemia Who Underwent Prolonged Periodic Fasting

Author

Bossi, L, Palumbo, C, Trojani, A, Melluso, A, Di Camillo, B, Beghini, A, Sarnataro, L, Cairoli, R, Bossi, Luca Emanuele, Palumbo, Cassandra, Trojani, Alessandra, Melluso, Agostina, Di Camillo, Barbara, Beghini, Alessandro, Sarnataro, Luca Maria, Cairoli, Roberto, Bossi, L, Palumbo, C, Trojani, A, Melluso, A, Di Camillo, B, Beghini, A, Sarnataro, L, Cairoli, R, Bossi, Luca Emanuele, Palumbo, Cassandra, Trojani, Alessandra, Melluso, Agostina, Di Camillo, Barbara, Beghini, Alessandro, Sarnataro, Luca Maria, and Cairoli, Roberto

Abstract

Background and Objectives: This study aimed to investigate the causes of continuous deep fluctuations in the absolute lymphocyte count (ALC) in an untreated patient with Chronic Lymphocytic Leukemia (CLL), who has had a favorable prognosis since the time of diagnosis. Up until now, the patient has voluntarily chosen to adopt a predominantly vegetarian and fruitarian diet, along with prolonged periods of total fasting (ranging from 4 to 39 days) each year. Materials and Methods: For this purpose, we decided to analyze the whole transcriptome profiling of peripheral blood (PB) CD19+ cells from the patient (#1) at different time-points vs. the same cells of five other untreated CLL patients who followed a varied diet. Consequently, the CLL patients were categorized as follows: the 1st group comprised patient #1 at 20 different time-points (16 time-points during nutrition and 4 time-points during fasting), whereas the 2nd group included only one time point for each of the patients (#2, #3, #4, #5, and #6) as they followed a varied diet. We performed microarray experiments using a powerful tool, the Affymetrix Human ClariomTM D Pico Assay, to generate high-fidelity biomarker signatures. Statistical analysis was employed to identify differentially expressed genes and to perform sample clustering. Results: The lymphocytosis trend in patient #1 showed recurring fluctuations since the time of diagnosis. Interestingly, we observed that approximately 4–6 weeks after the conclusion of fasting periods, the absolute lymphocyte count was reduced by about half. The gene expression profiling analysis revealed that nine genes were statistically differently expressed between the 1st group and the 2nd group. Specifically, IGLC3, RPS26, CHPT1, and PCDH9 were under expressed in the 1st group compared to the 2nd group of CLL patients. Conversely, IGHV3-43, IGKV3D-20, PLEKHA1, CYBB, and GABRB2 were over-expressed in the 1st group when compared to the 2nd group of CLL patients. Furthermore

Published
2023

6. A novel start-loss mutation of the SH2B3 gene in a family with myeloproliferative neoplasms

Author

Beghini, A, Leuzzi, L, Abazari, N, Bossi, L, Guido, V, Trojani, A, Cairoli, R, Beghini A, Leuzzi L, Abazari N, Bossi LE, Guido V, Trojani A, Cairoli R, Beghini, A, Leuzzi, L, Abazari, N, Bossi, L, Guido, V, Trojani, A, Cairoli, R, Beghini A, Leuzzi L, Abazari N, Bossi LE, Guido V, Trojani A, and Cairoli R

Abstract

The ever-increasing advances in high-throughput sequencing have broadened our understanding of the genetic pathogenesis of Philadelphia-negative myeloproliferative neoplasms (MPNs). Convergent studies have shown that MPN driver mutations associate with additional mutations found in genes coding for negative regulators of the JAK/STAT signaling, including the SH2B3 (SH2B-adaptor protein 3, also known as LNK). Here, we describe a novel heterozygous start-loss mutation of the SH2B3 gene (c.3G>A, SH2B3M?) in a consanguineous family characterized by recurrent early onset of JAK2V617F-positive MPNs. The model represented by this pedigree suggests that the SH2B3 could be a predisposing mutation that facilitates the acquisition of driver mutations.

Published
2022

7. 'Efficient Strategies for the Reuse of Surgical and FFP2/ KN95 Face Masks during the COVID-19 Pandemic: Home-Made and Ecological Choices for the Community'

Author

Bossi Luca, E, Trojani, A, Melluso, A, Bruzzone, A, Accarino, F, Cairoli, R, Bossi Luca Emanuele, Trojani A, Melluso A, Bruzzone AG, Accarino F, Cairoli R, Bossi Luca, E, Trojani, A, Melluso, A, Bruzzone, A, Accarino, F, Cairoli, R, Bossi Luca Emanuele, Trojani A, Melluso A, Bruzzone AG, Accarino F, and Cairoli R

Abstract

The SARS CoV-2 is responsible for the severe acute respiratory syndrome (COVID-19) which has claimed numerous victims worldwide. The main symptoms reported in the scientific literature are represented by fever, cough, gastrointestinal disturbances, dysgeusia, and anosmia but currently the symptomatology is not clear, yet. The symptoms vary from one individual to another one, depending mostly on the age of the patients and their co-morbidities. Wearing surgical or FFP2/KN-95 face masks block the interpersonal transmissibility of the droplets containing the virus which are produced during speaking, breathing or coughing. We pondered the regeneration of this personal protective equipment in order to reduce the costs and the biological waste released into the environment. In our paper, we have described four strategies for the decontamination of surgical and FFP2/KN95 face masks. The steam iron and the washing machine are easily reproducible at home, while the thermostatically controlled bath and the autoclave require more advanced structures such as hospitals or scientific institutes. The regeneration methods ensure that both surgical and FFP2/ KN95 face masks maintain the same characteristics of the unused ones. After the regeneration process, we demonstrated the conservation of the structural proprieties of the polypropylene fibers of both masks by light microscope. The microbiological analyses of both regenerated masks showed the absence of the main pathogens that can infect the nasopharyngeal tract. Moreover, we showed that both regenerated surgical and FFP2/KN95 face masks maintained their waterproof properties. Finally, we demonstrated that the regenerated FFP2/KN95 face masks maintained their adequate fit by the qualitative fit testing.

Published
2022

8. Homotopy double copy of noncommutative gauge theories

Author

Szabo, Richard J., Trojani, Guillaume, Szabo, Richard J., and Trojani, Guillaume

Abstract

We discuss the double copy formulation of Moyal-Weyl type noncommutative gauge theories from the homotopy algebraic perspective of factorisations of $L_\infty$-algebras. We define new noncommutative scalar field theories with rigid colour symmetries taking the role of the zeroth copy, where the deformed colour algebra plays the role of a kinematic algebra; some of these theories have a trivial classical limit but exhibit colour-kinematics duality, from which we construct the double copy theory explicitly. We show that noncommutative gauge theories exhibit a twisted form of colour-kinematics duality, which we use to show that their double copies match with the commutative case. We illustrate this explicitly for Chern-Simons theory, and also for Yang-Mills theory where we obtain a modified Kawai-Lewellen-Tye relation whose momentum kernel is linked to a binoncommutative biadjoint scalar theory. We reinterpret rank one noncommutative gauge theories as double copy theories, and discuss how our findings tie in with recent discussions of Moyal-Weyl deformations of self-dual Yang-Mills theory and gravity., Comment: 78 pages, 1 figure; v2: new concluding section added; Contribution to the Special Issue of Symmetry on "Quantum Geometry and Symmetries of String Theory"

Published
2023

10. Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study

Author

Pungolino, E, D'Adda, M, De Canal, G, Trojani, A, Perego, A, Elena, C, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Artale, S, Anghilieri, M, Molteni, A, Caramella, M, Baruzzo, G, Nichelatti, M, Di Camillo, B, Cairoli, R, Pungolino E, D'adda M, De Canal G, Trojani A, Perego A, Elena C, Lunghi F, Turrini M, Borin L, Iurlo A, Latargia ML, Carraro MC, Spina F, Artale S, Anghilieri M, Molteni A, Caramella M, Baruzzo G, Nichelatti M, Di Camillo B, Cairoli R, Pungolino, E, D'Adda, M, De Canal, G, Trojani, A, Perego, A, Elena, C, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Artale, S, Anghilieri, M, Molteni, A, Caramella, M, Baruzzo, G, Nichelatti, M, Di Camillo, B, Cairoli, R, Pungolino E, D'adda M, De Canal G, Trojani A, Perego A, Elena C, Lunghi F, Turrini M, Borin L, Iurlo A, Latargia ML, Carraro MC, Spina F, Artale S, Anghilieri M, Molteni A, Caramella M, Baruzzo G, Nichelatti M, Di Camillo B, and Cairoli R

Abstract

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in-vivo activity and timecourse of first-line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty-seven CP-CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per-Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK-STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.

Published
2021

11. The ERK1/2 Regulator WNK2 Shows Novel Alternative Splicing Aberrations That Support Tumor Growth in MYD88 Mutated Waldenstrom's Macroglobulinemia

Author

Guerrera, M, Liu, X, Morelli, E, Richardson, K, Tsakmaklis, N, Kofides, A, Munshi, M, Liu, S, Yang, G, Patterson, C, Castillo, J, Sarosiek, S, Flynn, C, Meid, K, Gustine, J, Branagan, A, Trojani, A, Tedeschi, A, Cairoli, R, Sewastianik, T, Carrasco, R, Anderson, K, Munshi, N, Treon, S, Hunter, Z, Guerrera, ML, Liu, SR, Patterson, CJ, Castillo, JJ, Flynn, CA, Branagan, AR, Carrasco, RD, Anderson, KC, Munshi, NC, Treon, SP, Hunter, ZR, Guerrera, M, Liu, X, Morelli, E, Richardson, K, Tsakmaklis, N, Kofides, A, Munshi, M, Liu, S, Yang, G, Patterson, C, Castillo, J, Sarosiek, S, Flynn, C, Meid, K, Gustine, J, Branagan, A, Trojani, A, Tedeschi, A, Cairoli, R, Sewastianik, T, Carrasco, R, Anderson, K, Munshi, N, Treon, S, Hunter, Z, Guerrera, ML, Liu, SR, Patterson, CJ, Castillo, JJ, Flynn, CA, Branagan, AR, Carrasco, RD, Anderson, KC, Munshi, NC, Treon, SP, and Hunter, ZR

Published
2022

12. PH plus STEM CELLS (SCS) IN CHRONIC MYELOID LEUKEMIA (CML): TO ERADICATE OR NOT TO ERADICATE, THIS IS THE QUESTION

Author

Pungolino, E, D'Adda, M, Trojani, A, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Bossi, L, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Pioltelli, M, Rossi, G, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Bossi LE, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro MC, Di Camillo B, Gramegna D, Pioltelli ML, Rossi G, Morra E, Cairoli R, Pungolino, E, D'Adda, M, Trojani, A, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Bossi, L, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Pioltelli, M, Rossi, G, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Bossi LE, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro MC, Di Camillo B, Gramegna D, Pioltelli ML, Rossi G, Morra E, and Cairoli R

Published
2019

13. Transmembrane receptors, cytoskeleton and cell cycle genes were progressively deregulated in the bone marrow CD19+ and CD138+ cells of patientswwith Waldenstrom's macroglolubinemia (WM) vs. Subjects with IgM monoclonal gammopathy of undetermined significance igmmgus vs. Healthy subjects

Author

Trojani, A, Tedeschi, A, Frustaci, A, Deodato, M, Bossi, L, Di Camillo, B, Montillo, M, Morra, E, Cairoli, R, Trojani A., Tedeschi A., Frustaci A.M., Deodato M., Bossi L.E., Di Camillo B., Montillo M., Morra E., Cairoli R, Trojani, A, Tedeschi, A, Frustaci, A, Deodato, M, Bossi, L, Di Camillo, B, Montillo, M, Morra, E, Cairoli, R, Trojani A., Tedeschi A., Frustaci A.M., Deodato M., Bossi L.E., Di Camillo B., Montillo M., Morra E., and Cairoli R

Published
2019

14. IDENTIFICAZIONE DI MIRNA E GENI TARGET NELL’ANALISI TRASCRITTOMICA DELLE CELLULE CD34+/LIN- DI PAZIENTI CON LEUCEMIA MIELOIDE CRONICA IN FASE CRONICA DOPO 12 MESI DI TERAPIA CON NILOTINIB

Author

Trojani, A, Pungolino, E, Dal Molin, A, Bossi, L, Rossi, G, D'Adda, M, Perego, A, Elena, C, Turrini, M, Borin, L, Bucelli, C, Malato, S, Carraro, M, Spina, F, Latargia, M, Artale, S, Spedini, P, Anghilieri, M, Di Camillo, B, Baruzzo, G, De Canal, G, Iurlo, A, Morra, E, Cairoli, R, Trojani A, Pungolino E, Dal Molin A, Bossi LE, Rossi G, D'Adda M, Perego A, Elena C, Turrini M, Borin L, Bucelli C, Malato S, Carraro MC, Spina F, Latargia ML, Artale S, Spedini P, Anghilieri M, Di Camillo B, Baruzzo G, De Canal G, Iurlo A, Morra E, Cairoli R, Trojani, A, Pungolino, E, Dal Molin, A, Bossi, L, Rossi, G, D'Adda, M, Perego, A, Elena, C, Turrini, M, Borin, L, Bucelli, C, Malato, S, Carraro, M, Spina, F, Latargia, M, Artale, S, Spedini, P, Anghilieri, M, Di Camillo, B, Baruzzo, G, De Canal, G, Iurlo, A, Morra, E, Cairoli, R, Trojani A, Pungolino E, Dal Molin A, Bossi LE, Rossi G, D'Adda M, Perego A, Elena C, Turrini M, Borin L, Bucelli C, Malato S, Carraro MC, Spina F, Latargia ML, Artale S, Spedini P, Anghilieri M, Di Camillo B, Baruzzo G, De Canal G, Iurlo A, Morra E, and Cairoli R

Published
2019

15. Progressive Down Regulation of JAK-STAT, Cell Cycle, and ABC Transporter Genes in CD34+/Lin- Cells of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients at Diagnosis Vs. 12 Months of Nilotinib Treatment Vs. Healthy Subjects

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Bossi, L, Baruzzo, G, Di Camillo, B, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Bossi L.E., Baruzzo G., Di Camillo B., Perego A., Turrini M., Elena C., Borin L.M., Iurlo A., Malato S., Spina F., Latargia M.L., Spedini P., Artale S., Anghilieri M., Carraro M.C., Bucelli C., De Canal G., Morra E., Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Bossi, L, Baruzzo, G, Di Camillo, B, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Bossi L.E., Baruzzo G., Di Camillo B., Perego A., Turrini M., Elena C., Borin L.M., Iurlo A., Malato S., Spina F., Latargia M.L., Spedini P., Artale S., Anghilieri M., Carraro M.C., Bucelli C., De Canal G., Morra E., and Cairoli R

Published
2019

16. FZD6 triggers Wnt–signalling driven by WNT10BIVS1 expression and highlights new targets in T-cell acute lymphoblastic leukemia

Author

Adriana, C, Giovanni, G, Marco, N, Jessica, G, Ilaria, E, Gianluigi, R, Alessandra, T, Giorgio, V, Barbara Di, C, Cairoli, R, Alessandro, B, Adriana Cassaro, Giovanni Grillo, Marco Notaro, Jessica Gliozzo, Ilaria Esposito, Gianluigi Reda, Alessandra Trojani, Giorgio Valentini, Barbara Di Camillo, Cairoli Roberto, Alessandro Beghini, Adriana, C, Giovanni, G, Marco, N, Jessica, G, Ilaria, E, Gianluigi, R, Alessandra, T, Giorgio, V, Barbara Di, C, Cairoli, R, Alessandro, B, Adriana Cassaro, Giovanni Grillo, Marco Notaro, Jessica Gliozzo, Ilaria Esposito, Gianluigi Reda, Alessandra Trojani, Giorgio Valentini, Barbara Di Camillo, Cairoli Roberto, and Alessandro Beghini

Abstract

Wnt/Fzd signaling has been implicated in hematopoietic stem cell maintenance and in acute leukemia establishment. In our previous work, we described a recurrent rearrangement involving the WNT10B locus (WNT10BR), characterized by the expression of WNT10BIVS1 transcript variant, in acute myeloid leukemia. To determine the occurrence of WNT10BR in T-cell acute lymphoblastic leukemia (T-ALL), we retrospectively analyzed an Italian cohort of patients (n = 20) and detected a high incidence (13/20) of WNT10BIVS1 expression. To address genes involved in WNT10B molecular response, we have designed a Wnt-targeted RNA sequencing panel. Identifying Wnt agonists and antagonists, it results that the expression of FZD6, LRP5, and PROM1 genes stands out in WNT10BIVS1 positive patients compared to negative ones. Using MOLT4 and MUTZ-2 as leukemic cell models, which are characterized by the expression of WNT10BIVS1, we have observed that WNT10B drives major Wnt activation to the FZD6 receptor complex through receipt of ligand. Additionally, short hairpin RNAs (shRNAs)-mediated gene silencing and small molecule-mediated inhibition of WNTs secretion have been observed to interfere with the WNT10B/FZD6 interaction. We have therefore identified that WNT10BIVS1 knockdown, or pharmacological interference by the LGK974 porcupine (PORCN) inhibitor, reduces WNT10B/FZD6 protein complex formation and significantly impairs intracellular effectors and leukemic expansion. These results describe the molecular circuit induced by WNT10B and suggest WNT10B/FZD6 as a new target in the T-ALL treatment strategy.

Published
2021

17. Identification of a candidate gene set signature for the risk of progression in igm mgus to smoldering/symptomatic waldenström macroglobulinemia (Wm) by a comparative transcriptome analysis of b cells and plasma cells

Author

Alessandra, T, Barbara Di, C, Luca Emanuele, B, Livia, L, Antonino, G, Anna Maria, F, Marina, D, Giulia, Z, Alessandro, B, Cairoli, R, Alessandra Trojani, Barbara Di Camillo, Luca Emanuele Bossi, Livia Leuzzi, Antonino Greco, Alessandra Tedeschi, Anna Maria Frustaci, Marina Deodato, Giulia Zamprogna, Alessandro Beghini, Cairoli Roberto, Alessandra, T, Barbara Di, C, Luca Emanuele, B, Livia, L, Antonino, G, Anna Maria, F, Marina, D, Giulia, Z, Alessandro, B, Cairoli, R, Alessandra Trojani, Barbara Di Camillo, Luca Emanuele Bossi, Livia Leuzzi, Antonino Greco, Alessandra Tedeschi, Anna Maria Frustaci, Marina Deodato, Giulia Zamprogna, Alessandro Beghini, and Cairoli Roberto

Abstract

Waldenström Macroglobulinemia (WM) is a B-cell lymphoma characterized by the precursor condition IgM monoclonal gammopathies of undetermined significance (IgM MGUS). We performed a gene expression profiling study to compare the transcriptome signatures of bone marrow (BM) B-cells and plasma cells of 36 WM patients, 13 IgM MGUS cases, and 7 healthy subjects used as controls (CTRLs) by Affymetrix microarray. We determined 2038 differentially expressed genes (DEGs) in CD19+ cells and 29 DEGs genes in CD138+ cells, respectively. The DEGs identified in B-cells were associated with KEGG pathways, mainly involved in hematopoietic cell lineage antigens, cell adhesion/focal adhesion/transmembrane proteins, adherens junctions, Wnt-signaling pathway, BCR-signaling pathway, calcium signaling pathway, complement/coagulation cascade, platelet activation, cytokine-cytokine receptor interactions, and signaling pathways responsible for cell cycle, apoptosis, proliferation and survival. In conclusion, we showed the deregulation of groups of genes belonging to KEGG pathways in the comparison among WM vs. IgM MGUS vs. CTRLs in B-cells. Interestingly, a small set of genes in B-cells displayed a common transcriptome expression profile between WM and IgM MGUS compared to CTRLs, suggesting its possible role in the risk of transformation of IgM MGUS to WM.

Published
2021

20. Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'Adda M, Lodola M, Di Camillo B, Perego A, Turrini M, Orlandi E, Borin L, Iurlo A, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, De Canal G, Morra E, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'Adda M, Lodola M, Di Camillo B, Perego A, Turrini M, Orlandi E, Borin L, Iurlo A, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, De Canal G, Morra E, and Cairoli R

Abstract

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib.

Published
2018

21. Nilotinib induced bone marrow CD34+/lin–Ph+ cells early clearance in newly diagnosed CP-chronic myeloid leukemia

Author

Pungolino, E, Rossi, G, De Canal, G, Trojani, A, D'Adda, M, Perego, A, Orlandi, E, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Lodola, M, Artale, S, Anghilieri, M, Spedini, P, Cantoni, S, Di Camillo, B, Morra, E, Cairoli, R, Pungolino E., Rossi G., De Canal G., Trojani A., D'adda M., Perego A., Orlandi E. M., Lunghi F., Turrini M., Borin L., Iurlo A., Latargia M. L., Carraro M. C., Spina F., Lodola M., Artale S., Anghilieri M., Spedini P., Cantoni S., Di Camillo B., Morra E., Cairoli R., Pungolino, E, Rossi, G, De Canal, G, Trojani, A, D'Adda, M, Perego, A, Orlandi, E, Lunghi, F, Turrini, M, Borin, L, Iurlo, A, Latargia, M, Carraro, M, Spina, F, Lodola, M, Artale, S, Anghilieri, M, Spedini, P, Cantoni, S, Di Camillo, B, Morra, E, Cairoli, R, Pungolino E., Rossi G., De Canal G., Trojani A., D'adda M., Perego A., Orlandi E. M., Lunghi F., Turrini M., Borin L., Iurlo A., Latargia M. L., Carraro M. C., Spina F., Lodola M., Artale S., Anghilieri M., Spedini P., Cantoni S., Di Camillo B., Morra E., and Cairoli R.

Published
2018

22. Combining Imatinib-Following-Nilotinib Treatment in First Line Therapy for Chronic Phase Chronic Myeloid Leukemia. Update from the PhilosoPhi34 Study at 24 Months of Follow-up

Author

Pioltelli, M, Pungolino, E, D'Adda, M, Elena, C, Borin, L, Perego, A, Malato, S, Spina, F, Artale, S, Carraro, M, Orofino, N, Anghilieri, M, Farina, M, Latargia, M, Iurlo, A, Trojani, A, Turrini, M, Caramella, M, Spedini, P, Rossi, G, Morra, E, Cairoli, R, Pioltelli ML, Pungolino E, D'adda M, Elena C, Borin LM, Perego A, Malato S, Spina F, Artale S, Carraro M, Orofino N, Anghilieri M, Farina M, Latargia ML, Iurlo A, Trojani A, Turrini M, Caramella M, Spedini P, Rossi G, Morra E, Cairoli R, Pioltelli, M, Pungolino, E, D'Adda, M, Elena, C, Borin, L, Perego, A, Malato, S, Spina, F, Artale, S, Carraro, M, Orofino, N, Anghilieri, M, Farina, M, Latargia, M, Iurlo, A, Trojani, A, Turrini, M, Caramella, M, Spedini, P, Rossi, G, Morra, E, Cairoli, R, Pioltelli ML, Pungolino E, D'adda M, Elena C, Borin LM, Perego A, Malato S, Spina F, Artale S, Carraro M, Orofino N, Anghilieri M, Farina M, Latargia ML, Iurlo A, Trojani A, Turrini M, Caramella M, Spedini P, Rossi G, Morra E, and Cairoli R

Published
2018

23. Identification of genes differently expressed between bone marrow CD34+/LIN-cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs 12 months of first-line nilotinib treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Bucelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Lodola M., Di Camillo B., Perego A., Turrini M., Orlandi E., Borin L., Iurlo A., Bucelli C., Malato S., Spina F., Latargia M.L., Lanza F., Artale S., Anghilieri M., Carraro M.C., De Canal G., Morra E., Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Bucelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, Cairoli, R, Trojani A., Pungolino E., Rossi G., D'Adda M., Lodola M., Di Camillo B., Perego A., Turrini M., Orlandi E., Borin L., Iurlo A., Bucelli C., Malato S., Spina F., Latargia M.L., Lanza F., Artale S., Anghilieri M., Carraro M.C., De Canal G., Morra E., and Cairoli R

Published
2018

24. Nilotinib Deregulates Cell Cycle Checkpoints, ABC Transporters Genes and JAK-STAT Signaling Pathway of CD34+/Lin- Cells in Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients after 12 Months of Treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Dal Molin, A, Baruzzo, G, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Cristina, C, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'adda M, Lodola M, Dal Molin A, Baruzzo G, Perego A, Turrini M, Elena C, Borin LM, Iurlo A, Malato S, Spina F, Latargia ML, Spedini P, Artale S, Anghilieri M, Cristina CM, Bucelli C, De Canal G, Morra E, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Dal Molin, A, Baruzzo, G, Perego, A, Turrini, M, Elena, C, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Spedini, P, Artale, S, Anghilieri, M, Cristina, C, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Trojani A, Pungolino E, Rossi G, D'adda M, Lodola M, Dal Molin A, Baruzzo G, Perego A, Turrini M, Elena C, Borin LM, Iurlo A, Malato S, Spina F, Latargia ML, Spedini P, Artale S, Anghilieri M, Cristina CM, Bucelli C, De Canal G, Morra E, and Cairoli R

Published
2018

25. Jak-2 and Nfkbia Gene Expression Play a Strategic Role in Chronic Myeloid Leukemia (CML) Molecular Response during Early Nilotinib Treatment: The PhilosoPhi34 Data

Author

Pungolino, E, D'Adda, M, Trojani, A, Perego, D, Pioltelli, M, Rossi, G, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Lodola, M, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego D, Pioltelli ML, Rossi G, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Lodola M, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro M, Di Camillo B, Gramegna D, Morra E, Cairoli R, Pungolino, E, D'Adda, M, Trojani, A, Perego, D, Pioltelli, M, Rossi, G, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Lodola, M, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Morra, E, Cairoli, R, Pungolino E, D'adda M, Trojani A, Perego D, Pioltelli ML, Rossi G, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Lodola M, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro M, Di Camillo B, Gramegna D, Morra E, and Cairoli R

Published
2018

26. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial

Author

Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, Vaccaro O., Masulli M., Nicolucci A., Bonora E., Del Prato S., Maggioni A. P., Rivellese A. A., Squatrito S., Giorda C. B., Sesti G., Mocarelli P., Lucisano G., Sacco M., Signorini S., Cappellini F., Perriello G., Babini A. C., Lapolla A., Gregori G., Giordano C., Corsi L., Buzzetti R., Clemente G., Di Cianni G., Iannarelli R., Cordera R., La Macchia O., Zamboni C., Scaranna C., Boemi M., Iovine C., Lauro D., Leotta S., Dall'Aglio E., Cannarsa E., Tonutti L., Pugliese G., Bossi A. C., Anichini R., Dotta F., Di Benedetto A., Citro G., Antenucci D., Ricci L., Giorgino F., Santini C., Gnasso A., De Cosmo S., Zavaroni D., Vedovato M., Consoli A., Calabrese M., di Bartolo P., Fornengo P., Riccardi G., D'Angelo F., Giansanti R., Tanase L., Lanari L., Testa I., Pancani F., Ranchelli A., Vagheggi P., Scatona A., Fontana L., Laviola L., Tarantino L., Ippolito C., Gigantelli V., Manicone M., Conte E., Trevisan R., Rota R., Dodesini A. R., Reggiani G. M., Montesi L., Mazzella N., Forlani G., Caselli C., Di Luzio R., Mazzotti A., Aiello A., Barrea A., Musto A., D'Amico F., Sinagra T., Longhitano S., Trowpea V., Sparti M., Italia S., Lisi E., Grasso G., Pezzino V., Insalaco F., Carallo C., Scicchitano C., De Franceschi M. S., Calbucci G., Ripani R., Cuneo G., Corsi S., Romeo F., Lesina A., Comoglio M., Bonetto C., Robusto A., Nada E., Asprino V., Cetraro R., Impieri M., Lucchese G., Donnarumma G., Tizio B., Lenza L., Paraggio P., Tomasi F., Dozio N., Scalambra E., Mannucci E., Lamanna C., Cignarelli M., Macchia O. L., Fariello S., Sorrentino M. R., Franzetti I., Radin R., Annunziata F., Bonabello L. A., Durante A., Dolcino M., Gallo F., Mazzucchelli C., Aleo A., Melga P., Briatore L., Maggi D., Storace D., Cecoli F., D'Ugo E., Pupillo M., Baldassarre M. P. A., Salvati F., Minnucci A., De Luca A., Zugaro A., Santarelli L., Bosco A., Petrella V., La Verghetta G. G., D'Andrea S., Giuliani A. E., Polidoro W. L., Sperandio A., Sciarretta F., Pezzella A., Carlone A., Potenziani S., Venditti C., Foffi C., Carbone S., Cipolloni L., Moretti C., Leto G., Serra R., Petrachi F., Romano I., Lacaria E., Russo L., Goretti C., Sannino C., Dolci M., Bruselli L., Mori M. L., Baccetti F., Del Freo M., Cucinotta D., Giunta L., Ruffo M. C., Cannizzaro D., Pintaudi B., Perrone G., Pata P., Ragonese F., Lettina G., Mancuso T., Coppolino A., Piatti P. M., Monti L., Stuccillo M., Lucotti P., Setola M., Crippa G. V., Loi C., Oldani M., Bottalico M. L., Pellegata B., Bonomo M., Menicatti L. S. M., Resi V., Bertuzzi F., Disoteo E. O., Pizzi G., Annuzzi G., Capaldo B., Nappo R., Auciello S. M., Turco A. A., Costagliola L., Corte G. D., Vallefuoco P., Nappi F., Vitale M., Cocozza S., Ciano O., Massimino E., Garofalo N., Avogaro A., Guarneri G., Fedele D., Sartore G., Chilelli N. C., Burlina S., Bonsembiante B., Galluzzo A., Torregrossa V., Mancastroppa G., Arsenio L., Cioni F., Caronna S., Papi M., Santeusanio F., Calagreti G., Timi A., Tantucci A., Marino C., Ginestra F., Di Biagio R., Taraborelli M., Miccoli R., Bianchi C., Garofolo M., Politi K. S., Penno G., Livraga S., Calzoni F., Mancastroppa G. L. F., Corsini E., Tedeschi A., Gagliano M. S., Ippolito G., Salutini E., Cervellino F., Natale M., Salvatore V., Zampino A., Sinisi R., Arcangeli A., Zogheri A., Guizzotti S., Longo R., Pellicano F., Scolozzi P., Termine S., Luberto A., Ballardini G., Trojani C., Mazzuca P., Bruglia M., Ciamei M., Genghini S., Zannoni C., Rangel G., Salvi L., Zappaterreno A., Cordone S., Simonelli P., Meggiorini M., Frasheri A., Di Pippo C., Maglio C., Mazzitelli G., Rinaldi M. E., Galli A., Romano M., D'Angelo P., Suraci C., Bacci S., Palena A. P., Genovese S., Mancino M., Rondinelli M., Capone F., Calabretto E., Bulgheroni M., Bucciarelli L., Ceccarelli E., Fondelli C., Santacroce C., Guarino E., Nigi L., Lalli C., Di Vizia G., Scarponi M., Montani V., Di Bernardino P., Romagni P., Dolcetti K., Forte E., Tamburo L., Perin P. C., Prinzis T., Gruden G., Bruno G., Zucco C., Perotta M., Marena S., Monsignore S., Panero F., Ponzi F., Carpinteri R., Casagrande M. L., Coletti M. F., Balini A., Filopanti M., Madaschi S., Pulcina A., Grimaldi F., Venturini G., Agus S., Pagnutti S., Guidotti F., Cavarape A., Cigolini M., Pichiri I., Brangani C., Fainelli G., Tomasetto E., Zoppini G., Galletti A., Perrone D., Capra C., Bianchini F., Ceseri M., Di Nardo B., Sasso E., Bartolomei B., Suliman I., Fabbri G., Romano G., Maturo N., Nunziata G., Capobianco G., De Simone G., Villa V., Rota G., Pentangelo C., Carbonara O., Caiazzo G., Cutolo M., Sorrentino T., Mastrilli V., Amelia U., Masi S., Corigliano G., Gaeta I., Armentano V., Calatola P., Capuano G., Angiulli B., Auletta P., Petraroli E., Iodice C. E., Agrusta M., Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, Vaccaro O., Masulli M., Nicolucci A., Bonora E., Del Prato S., Maggioni A. P., Rivellese A. A., Squatrito S., Giorda C. B., Sesti G., Mocarelli P., Lucisano G., Sacco M., Signorini S., Cappellini F., Perriello G., Babini A. C., Lapolla A., Gregori G., Giordano C., Corsi L., Buzzetti R., Clemente G., Di Cianni G., Iannarelli R., Cordera R., La Macchia O., Zamboni C., Scaranna C., Boemi M., Iovine C., Lauro D., Leotta S., Dall'Aglio E., Cannarsa E., Tonutti L., Pugliese G., Bossi A. C., Anichini R., Dotta F., Di Benedetto A., Citro G., Antenucci D., Ricci L., Giorgino F., Santini C., Gnasso A., De Cosmo S., Zavaroni D., Vedovato M., Consoli A., Calabrese M., di Bartolo P., Fornengo P., Riccardi G., D'Angelo F., Giansanti R., Tanase L., Lanari L., Testa I., Pancani F., Ranchelli A., Vagheggi P., Scatona A., Fontana L., Laviola L., Tarantino L., Ippolito C., Gigantelli V., Manicone M., Conte E., Trevisan R., Rota R., Dodesini A. R., Reggiani G. M., Montesi L., Mazzella N., Forlani G., Caselli C., Di Luzio R., Mazzotti A., Aiello A., Barrea A., Musto A., D'Amico F., Sinagra T., Longhitano S., Trowpea V., Sparti M., Italia S., Lisi E., Grasso G., Pezzino V., Insalaco F., Carallo C., Scicchitano C., De Franceschi M. S., Calbucci G., Ripani R., Cuneo G., Corsi S., Romeo F., Lesina A., Comoglio M., Bonetto C., Robusto A., Nada E., Asprino V., Cetraro R., Impieri M., Lucchese G., Donnarumma G., Tizio B., Lenza L., Paraggio P., Tomasi F., Dozio N., Scalambra E., Mannucci E., Lamanna C., Cignarelli M., Macchia O. L., Fariello S., Sorrentino M. R., Franzetti I., Radin R., Annunziata F., Bonabello L. A., Durante A., Dolcino M., Gallo F., Mazzucchelli C., Aleo A., Melga P., Briatore L., Maggi D., Storace D., Cecoli F., D'Ugo E., Pupillo M., Baldassarre M. P. A., Salvati F., Minnucci A., De Luca A., Zugaro A., Santarelli L., Bosco A., Petrella V., La Verghetta G. G., D'Andrea S., Giuliani A. E., Polidoro W. L., Sperandio A., Sciarretta F., Pezzella A., Carlone A., Potenziani S., Venditti C., Foffi C., Carbone S., Cipolloni L., Moretti C., Leto G., Serra R., Petrachi F., Romano I., Lacaria E., Russo L., Goretti C., Sannino C., Dolci M., Bruselli L., Mori M. L., Baccetti F., Del Freo M., Cucinotta D., Giunta L., Ruffo M. C., Cannizzaro D., Pintaudi B., Perrone G., Pata P., Ragonese F., Lettina G., Mancuso T., Coppolino A., Piatti P. M., Monti L., Stuccillo M., Lucotti P., Setola M., Crippa G. V., Loi C., Oldani M., Bottalico M. L., Pellegata B., Bonomo M., Menicatti L. S. M., Resi V., Bertuzzi F., Disoteo E. O., Pizzi G., Annuzzi G., Capaldo B., Nappo R., Auciello S. M., Turco A. A., Costagliola L., Corte G. D., Vallefuoco P., Nappi F., Vitale M., Cocozza S., Ciano O., Massimino E., Garofalo N., Avogaro A., Guarneri G., Fedele D., Sartore G., Chilelli N. C., Burlina S., Bonsembiante B., Galluzzo A., Torregrossa V., Mancastroppa G., Arsenio L., Cioni F., Caronna S., Papi M., Santeusanio F., Calagreti G., Timi A., Tantucci A., Marino C., Ginestra F., Di Biagio R., Taraborelli M., Miccoli R., Bianchi C., Garofolo M., Politi K. S., Penno G., Livraga S., Calzoni F., Mancastroppa G. L. F., Corsini E., Tedeschi A., Gagliano M. S., Ippolito G., Salutini E., Cervellino F., Natale M., Salvatore V., Zampino A., Sinisi R., Arcangeli A., Zogheri A., Guizzotti S., Longo R., Pellicano F., Scolozzi P., Termine S., Luberto A., Ballardini G., Trojani C., Mazzuca P., Bruglia M., Ciamei M., Genghini S., Zannoni C., Rangel G., Salvi L., Zappaterreno A., Cordone S., Simonelli P., Meggiorini M., Frasheri A., Di Pippo C., Maglio C., Mazzitelli G., Rinaldi M. E., Galli A., Romano M., D'Angelo P., Suraci C., Bacci S., Palena A. P., Genovese S., Mancino M., Rondinelli M., Capone F., Calabretto E., Bulgheroni M., Bucciarelli L., Ceccarelli E., Fondelli C., Santacroce C., Guarino E., Nigi L., Lalli C., Di Vizia G., Scarponi M., Montani V., Di Bernardino P., Romagni P., Dolcetti K., Forte E., Tamburo L., Perin P. C., Prinzis T., Gruden G., Bruno G., Zucco C., Perotta M., Marena S., Monsignore S., Panero F., Ponzi F., Carpinteri R., Casagrande M. L., Coletti M. F., Balini A., Filopanti M., Madaschi S., Pulcina A., Grimaldi F., Venturini G., Agus S., Pagnutti S., Guidotti F., Cavarape A., Cigolini M., Pichiri I., Brangani C., Fainelli G., Tomasetto E., Zoppini G., Galletti A., Perrone D., Capra C., Bianchini F., Ceseri M., Di Nardo B., Sasso E., Bartolomei B., Suliman I., Fabbri G., Romano G., Maturo N., Nunziata G., Capobianco G., De Simone G., Villa V., Rota G., Pentangelo C., Carbonara O., Caiazzo G., Cutolo M., Sorrentino T., Mastrilli V., Amelia U., Masi S., Corigliano G., Gaeta I., Armentano V., Calatola P., Capuano G., Angiulli B., Auletta P., Petraroli E., Iodice C. E., and Agrusta M.

Abstract

Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50–75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2–3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15–45 mg) or a sulfonylurea (5–15 mg glibenclamide, 2–6 mg glimepiride, or 30–120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 p

Published
2017

27. Nilotinib interferes with cell cycle, ABC transporters and JAK-STAT signaling pathway in CD34+/lin- cells of patients with chronic phase chronic myeloid leukemia after 12 months of treatment

Author

Alessandra, T, Ester, P, Alessandra Dal, M, Milena, L, Giuseppe, R, Mariella, D, Alessandra, P, Chiara, E, Mauro, T, Lorenza, B, Cristina, B, Simona, M, Maria Cristina, C, Francesco, S, Maria Luisa, L, Salvatore, A, Pierangelo, S, Michela, A, Barbara Di, C, Giacomo, B, Gabriella De, C, Alessandra, I, Enrica, M, Cairoli, R, Alessandra Trojani, Ester Pungolino, Alessandra Dal Molin, Milena Lodola, Giuseppe Rossi, Mariella D’Adda, Alessandra Perego, Chiara Elena, Mauro Turrini, Lorenza Borin, Cristina Bucelli, Simona Malato, Maria Cristina Carraro, Francesco Spina, Maria Luisa Latargia, Salvatore Artale, Pierangelo Spedini, Michela Anghilieri, Barbara Di Camillo, Giacomo Baruzzo, Gabriella De Canal, Alessandra Iurlo, Enrica Morra, Cairoli R, Alessandra, T, Ester, P, Alessandra Dal, M, Milena, L, Giuseppe, R, Mariella, D, Alessandra, P, Chiara, E, Mauro, T, Lorenza, B, Cristina, B, Simona, M, Maria Cristina, C, Francesco, S, Maria Luisa, L, Salvatore, A, Pierangelo, S, Michela, A, Barbara Di, C, Giacomo, B, Gabriella De, C, Alessandra, I, Enrica, M, Cairoli, R, Alessandra Trojani, Ester Pungolino, Alessandra Dal Molin, Milena Lodola, Giuseppe Rossi, Mariella D’Adda, Alessandra Perego, Chiara Elena, Mauro Turrini, Lorenza Borin, Cristina Bucelli, Simona Malato, Maria Cristina Carraro, Francesco Spina, Maria Luisa Latargia, Salvatore Artale, Pierangelo Spedini, Michela Anghilieri, Barbara Di Camillo, Giacomo Baruzzo, Gabriella De Canal, Alessandra Iurlo, Enrica Morra, and Cairoli R

Abstract

Chronic myeloid leukemia (CML) is characterized by the constitutive tyrosine kinase activity of the oncoprotein BCR-ABL1 in myeloid progenitor cells that activates multiple signal transduction pathways leading to the leukemic phenotype. The tyrosine-kinase inhibitor (TKI) nilotinib inhibits the tyrosine kinase activity of BCR-ABL1 in CML patients. Despite the success of nilotinib treatment in patients with chronic-phase (CP) CML, a population of Philadelphia-positive (Ph+) quiescent stem cells escapes the drug activity and can lead to drug resistance. The molecular mechanism by which these quiescent cells remain insensitive is poorly understood. The aim of this study was to compare the gene expression profiling (GEP) of bone marrow (BM) CD34+/lin- cells from CP-CML patients at diagnosis and after 12 months of nilotinib treatment by microarray, in order to identify gene expression changes and the dysregulation of pathways due to nilotinib action. We selected BM CD34+/lin- cells from 78 CP-CML patients at diagnosis and after 12 months of first-line nilotinib therapy and microarray analysis was performed. GEP bioinformatic analyses identified 2,959 differently expressed probes and functional clustering determined some significantly enriched pathways between diagnosis and 12 months of nilotinib treatment. Among these pathways, we observed the under expression of 26 genes encoding proteins belonging to the cell cycle after 12 months of nilotinib treatment which led to the up-regulation of chromosome replication, cell proliferation, DNA replication, and DNA damage checkpoint at diagnosis. We demonstrated the under expression of the ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCD3 encoding proteins which pumped drugs out of the cells after 12 months of nilotinib. Moreover, GEP data demonstrated the deregulation of genes involved in the JAK-STAT signaling pathway. The down-regulation of JAK2, IL7, STAM, PIK3CA, PTPN11, RAF1, and SOS1 key genes after 12 months

Published
2019

28. DIFFERENT SETS OF GENES WERE ASSOCIATED TO THE MOLECULAR RESPONSE AFTER 3 AND 6 MONTHS OF FIRST-LINE NILOTINIB TREATMENT BY MICROARRAY OF CD34+/LIN- CELLS OF CHRONIC PHASE CML PATIENTS AT DIAGNOSIS

Author

Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Orlandi, E, Elena, C, Iurlo, A, Bucelli, C, Borin, L, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bertinato, E, Morra, E, Cairoli, R, Trojani A, Pungolino E, Lodola M, Di Camillo B, D'Adda M, Perego A, Turrini M, Orlandi E, Elena C, Iurlo A, Bucelli C, Borin L, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, Bertinato E, Morra E, Cairoli R, Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Orlandi, E, Elena, C, Iurlo, A, Bucelli, C, Borin, L, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bertinato, E, Morra, E, Cairoli, R, Trojani A, Pungolino E, Lodola M, Di Camillo B, D'Adda M, Perego A, Turrini M, Orlandi E, Elena C, Iurlo A, Bucelli C, Borin L, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, Bertinato E, Morra E, and Cairoli R

Published
2016

29. Genes and Pathways Dysregulated by Nilotinib Treatment in Bone Marrow CD34+/Lin- Cells of Patients with Chronic-Phase Chronic Myeloid Leukaemia

Author

Alessandra, T, Ester, P, Alessandra Dal, M, Milena, L, Gabriella De, C, Giuseppe, R, Mariella, D, Alessandra, P, Ester, O, Malato, S, Mauro, T, Lorenza, B, Alessandra, I, Maria Luisa, L, Maria Cristina, C, Francesco, S, Salvatore, A, Michela, A, Francesco, L, Enrica, M, Cairoli, R, Alessandra Trojani, Ester Pungolino, Alessandra Dal Molin, Milena Lodola, Gabriella De Canal, Giuseppe Rossi, Mariella D’Adda, Alessandra Perego, Ester Orlandi, Malato Simona, Mauro Turrini, Lorenza Borin, Alessandra Iurlo, Maria Luisa Latargia, Maria Cristina Carraro, Francesco Spina, Salvatore Artale, Michela Anghilieri, Francesco Lanza, Enrica Morra, Cairoli Roberto, Alessandra, T, Ester, P, Alessandra Dal, M, Milena, L, Gabriella De, C, Giuseppe, R, Mariella, D, Alessandra, P, Ester, O, Malato, S, Mauro, T, Lorenza, B, Alessandra, I, Maria Luisa, L, Maria Cristina, C, Francesco, S, Salvatore, A, Michela, A, Francesco, L, Enrica, M, Cairoli, R, Alessandra Trojani, Ester Pungolino, Alessandra Dal Molin, Milena Lodola, Gabriella De Canal, Giuseppe Rossi, Mariella D’Adda, Alessandra Perego, Ester Orlandi, Malato Simona, Mauro Turrini, Lorenza Borin, Alessandra Iurlo, Maria Luisa Latargia, Maria Cristina Carraro, Francesco Spina, Salvatore Artale, Michela Anghilieri, Francesco Lanza, Enrica Morra, and Cairoli Roberto

Published
2018

30. REL-Protocol PhilosoPhi34: An Open Label, Single Arm, Phase II Study of Nilotinib 300 Mg BID in Newly Diagnosed Chronic Phase Chronic Myeloid Leukaemia Patients, to Study the Disappearance of CD34+/Lin-Ph+ Cells from Bone Marrow during Treatment. Preliminary Data

Author

Pungolino, E, Rossi, G, Angela Mura, M, Perego, A, Maria Orlandi, E, Turrini, M, Borin, L, Adele Capucci, M, Iurlo, A, Trojani, A, D'Adda, M, Spina, F, De Canal, G, Luisa Pioltelli, M, Luisa Latargia, M, Pauli, S, Elena, C, Brusorio, S, Lanza, F, Malato, S, Anghilieri, M, C Carraro, M, Morra, E, Cairoli, R, Ester Pungolino, Giuseppe Rossi, Maria Angela Mura, Alessandra Perego, Ester Maria Orlandi, Mauro Turrini, Lorenza Borin, Maria Adele Capucci, Alessandra Iurlo, Alessandra Trojani, Mariella D'Adda, Francesco Spina, Gabriella De Canal, Maria Luisa Pioltelli, Maria Luisa Latargia, Sergio Pauli, Chiara Elena, Stefania Brusorio, Francesco Lanza, Simona Malato, Michela Anghilieri, Maria C Carraro, Enrica Morra, Roberto Cairoli, Pungolino, E, Rossi, G, Angela Mura, M, Perego, A, Maria Orlandi, E, Turrini, M, Borin, L, Adele Capucci, M, Iurlo, A, Trojani, A, D'Adda, M, Spina, F, De Canal, G, Luisa Pioltelli, M, Luisa Latargia, M, Pauli, S, Elena, C, Brusorio, S, Lanza, F, Malato, S, Anghilieri, M, C Carraro, M, Morra, E, Cairoli, R, Ester Pungolino, Giuseppe Rossi, Maria Angela Mura, Alessandra Perego, Ester Maria Orlandi, Mauro Turrini, Lorenza Borin, Maria Adele Capucci, Alessandra Iurlo, Alessandra Trojani, Mariella D'Adda, Francesco Spina, Gabriella De Canal, Maria Luisa Pioltelli, Maria Luisa Latargia, Sergio Pauli, Chiara Elena, Stefania Brusorio, Francesco Lanza, Simona Malato, Michela Anghilieri, Maria C Carraro, Enrica Morra, and Roberto Cairoli

Published
2015

31. Gene Expression Profiling of CD34+/Lin- Cells of Patients with Chronic Myeloid Leukemia at Diagnosis and after 12 Months of Nilotinib

Author

Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Artale, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Artale S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Artale, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Artale S, Morra E, and Pungolino E

Published
2014

32. GENE EXPRESSION PROFILING OF CD34+/LIN- CELLS OF PATIENTS WITH CHRONIC MYELOID LEUKEMIA AT DIAGNOSIS IDENTIFIES NEW GENES RELATED TO THE NUMBER OF CD34+/LIN- CELLS DURING NILOTINIB TREATMENT

Author

Trojani, A, Lodola, M, Di Camillo, B, Capucci, A, Cavalli, L, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Capucci A, Cavalli L, Perego A, Pogliani E, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Capucci, A, Cavalli, L, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Capucci A, Cavalli L, Perego A, Pogliani E, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, and Pungolino E

Published
2014

33. Microarray of Bone Marrow CD34+/Lin- Cells from Patients with Chronic Myeloid Leukemia (CML)

Author

Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, Pungolino E, Trojani, A, Lodola, M, Di Camillo, B, Rossi, G, Capucci, A, Perego, A, Pogliani, E, Orlandi, E, Iurlo, A, Malato, S, Corradini, P, Cairoli, R, Bregni, M, Pauli, S, Morra, E, Pungolino, E, Trojani A, Lodola M, Di Camillo B, Rossi G, Capucci A, Perego A, Pogliani EM, Orlandi E, Iurlo A, Malato S, Corradini P, Cairoli R, Bregni M, Pauli S, Morra E, and Pungolino E

Published
2014

34. Gene Expression Profiling and Cellularity of Bone Marrow CD34+/Lin- Cells of Patients with Chronic-Phase Chronic Myeloid Leukemia at Diagnosis Vs. 12 Months of First-Line Nilotinib Treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Orlandi, EM, Borin, LM, Latargia, ML, Carraro, MC, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, Cairoli, R, Orlandi, EM, Borin, LM, Latargia, ML, Carraro, MC, and Cairoli R

Published
2017

35. Preliminary Experience of Imatinib after Nilotinib in the First Line Treatment of Chronic Myeloid Leukemia

Author

Pungolino, E, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Borin, L, Iurlo, A, Artale, S, Latargia, M, Anghilieri, M, Malato, S, Trojani, A, Spina, F, Carraro, M, Pioltelli, M, Elena, C, Bucelli, C, Spedini, P, Rossi, G, Morra, E, Cairoli, R, D'adda M, Perego A, Orlandi, EM, Borin, LM, Latargia, ML, Carraro, MC, Pioltelli, ML, Pungolino, E, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Borin, L, Iurlo, A, Artale, S, Latargia, M, Anghilieri, M, Malato, S, Trojani, A, Spina, F, Carraro, M, Pioltelli, M, Elena, C, Bucelli, C, Spedini, P, Rossi, G, Morra, E, Cairoli, R, D'adda M, Perego A, Orlandi, EM, Borin, LM, Latargia, ML, Carraro, MC, and Pioltelli, ML

Published
2017

36. REL-PROTOCOL PHILOSOPHI34 CONFIRMS THAT NILOTINIB RAPIDLY INDUCES CD34+/LIN-PH+ CELLS DISAPPEARANCE IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA (CML) IN CHRONIC PHASE (CP)

Author

Pungolino, E, De Canal, G, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Trojani, A, Malato, S, Lodola, M, Borin, L, Iurlo, A, Artale, S, Spina, F, Pioltelli, M, Latargia, M, Brusorio, S, Elena, C, Lanza, F, Anghilieri, M, Carraro, M, Rossi, G, Morra, E, Cairoli, R, Orlandi, EM, Pioltelli, ML, Latargia, ML, Carraro, MC, Pungolino, E, De Canal, G, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Trojani, A, Malato, S, Lodola, M, Borin, L, Iurlo, A, Artale, S, Spina, F, Pioltelli, M, Latargia, M, Brusorio, S, Elena, C, Lanza, F, Anghilieri, M, Carraro, M, Rossi, G, Morra, E, Cairoli, R, Orlandi, EM, Pioltelli, ML, Latargia, ML, and Carraro, MC

Published
2016

37. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation

Author

Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, Morra, E, Trojani A, Ripamonti CB, Penco S, Beghini A, Nadali G, Di Bona E, Viola A, Castagnola C, Colapietro P, Grillo G, Pezzetti L, Ravelli E, Patrosso MC, Marocchi A, Cuneo A, Ferrara F, Lazzarino M, Pizzolo G, Cairoli R, Morra E., Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, Morra, E, Trojani A, Ripamonti CB, Penco S, Beghini A, Nadali G, Di Bona E, Viola A, Castagnola C, Colapietro P, Grillo G, Pezzetti L, Ravelli E, Patrosso MC, Marocchi A, Cuneo A, Ferrara F, Lazzarino M, Pizzolo G, Cairoli R, and Morra E.

Abstract

Background: Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. Patients and Methods: In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. Results: Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. Conclusion: These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.

Published
2008

38. Patient demographics and surgical characteristics in ACL revision: a comparison of French, Norwegian, and North American cohorts.

Author

Magnussen, Robert A, Magnussen, Robert A, Trojani, Christophe, Granan, Lars-Petter, Neyret, Philippe, Colombet, Philippe, Engebretsen, Lars, Wright, Rick W, Kaeding, Christopher C, MARS Group, SFA Revision ACL Group, Magnussen, Robert A, Magnussen, Robert A, Trojani, Christophe, Granan, Lars-Petter, Neyret, Philippe, Colombet, Philippe, Engebretsen, Lars, Wright, Rick W, Kaeding, Christopher C, MARS Group, and SFA Revision ACL Group

Abstract

PurposeThe goal of this paper is to compare patient factors, intra-operative findings, and surgical techniques between patients followed in large cohorts in France, Norway, and North America.MethodsData collected on 2,286 patients undergoing revision anterior cruciate ligament reconstruction (ACLR) were obtained. These data included 1,216 patients enrolled in the Multicenter ACL Revision Study (MARS) in North America, 793 patients undergoing revision ACLR and recorded in the Norwegian Knee Ligament Registry (NKLR), and 277 patients recorded in the revision ACL database of the Société Française d'Arthroscopie (SFA) in France. Data collected from each database included patient demographics (age, sex, height, and weight), graft choice and reason for failure of the primary ACLR, time from primary to revision ACLR, pre-revision patient-reported outcome scores (Knee Injury and Osteoarthritis Outcome Score, subjective International Knee Documentation Committee), associated intra-articular findings and treatments at revision, and graft choice for revision reconstruction.ResultsPatient demographics in the three databases were relatively similar. Graft choice for primary and revision ACLR varied significantly, with more allografts used in the MARS cohort. Hamstring autograft was favoured in the NKRL, while bone-patellar tendon-bone autograft was most common in the SFA cohort. Reasons for failure of the primary ACLR were comparable, with recurrent trauma noted in 46-56 % of patients in each of the three cohorts. Technical error was cited in 44-51 % of patients in the MARS and SFA cohorts, but was not clearly elucidated in the NKLR cohort. Biologic failure of the primary graft was more common in the MARS cohort. Differences in associated intra-articular findings were noted at the time of revision ACLR, with significantly more high-grade cartilage lesions noted in the MARS group.ConclusionsSignificant differences exist between patient populations followed in revision A

Published
2015

39. GEP Analyses of Bone Marrow CD34+/Lin-Cells of Chronic Phase CML Patients at Diagnosis Identified Different Sets of Genes Associated to the Molecular Response after 3 and 6 Months of First-Line Nilotinib Treatment

Author

Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Elena, C, Iurlo, A, Buccelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Pauli, S, Anghilieri, M, Carraro, M, Morra, E, Cairoli, R, Latargia, ML, Carraro, MC, Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Elena, C, Iurlo, A, Buccelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Pauli, S, Anghilieri, M, Carraro, M, Morra, E, Cairoli, R, Latargia, ML, and Carraro, MC

Published
2015

40. Gene Expression Profiling of Waldenström's Macroglobulinemia vs. IgM Monoclonal Gammopathy of Undetermined Significance

Author

Alessandra, T, Antonino, G, Milena, L, Barbara Di, C, Anna Maria, F, Cairoli, R, Enrica, M, Alessandra Trojani, Antonino Greco, Alessandra Tedeschi, Milena Lodola, Barbara Di Camillo, Anna Maria Frustaci, Cairoli Roberto, Enrica Morra, Alessandra, T, Antonino, G, Milena, L, Barbara Di, C, Anna Maria, F, Cairoli, R, Enrica, M, Alessandra Trojani, Antonino Greco, Alessandra Tedeschi, Milena Lodola, Barbara Di Camillo, Anna Maria Frustaci, Cairoli Roberto, and Enrica Morra

Published
2014

41. Robust subsampling

Author

Camponovo, Lorenzo, Scaillet, Olivier, Trojani, Fabio, Camponovo, Lorenzo, Scaillet, Olivier, and Trojani, Fabio

Abstract

We characterize the robustness of subsampling procedures by deriving a formula for the breakdown point of subsampling quantiles. This breakdown point can be very low for moderate subsampling block sizes, which implies the fragility of subsampling procedures, even when they are applied to robust statistics. This instability arises also for data driven block size selection procedures minimizing the minimum confidence interval volatility index, but can be mitigated if a more robust calibration method can be applied instead. To overcome these robustness problems, we introduce a consistent robustsubsampling procedure for M-estimators and derive explicit subsampling quantile breakdown point characterizations for MM-estimators in the linear regression model. Monte Carlo simulations in two settings where the bootstrap fails show the accuracy and robustness of the robustsubsampling relative to the subsampling.

Published
2012

42. Limits of learning about a categorical latent variable under prior near-ignorance

Author

Piatti, Alberto, Zaffalon, Marco, Trojani, Fabio, Hutter, Marcus, Piatti, Alberto, Zaffalon, Marco, Trojani, Fabio, and Hutter, Marcus

Abstract

In this paper, we consider the coherent theory of (epistemic) uncertainty of Walley, in which beliefs are represented through sets of probability distributions, and we focus on the problem of modeling prior ignorance about a categorical random variable. In this setting, it is a known result that a state of prior ignorance is not compatible with learning. To overcome this problem, another state of beliefs, called near-ignorance, has been proposed. Near-ignorance resembles ignorance very closely, by satisfying some principles that can arguably be regarded as necessary in a state of ignorance, and allows learning to take place. What this paper does, is to provide new and substantial evidence that also near-ignorance cannot be really regarded as a way out of the problem of starting statistical inference in conditions of very weak beliefs. The key to this result is focusing on a setting characterized by a variable of interest that is latent. We argue that such a setting is by far the most common case in practice, and we provide, for the case of categorical latent variables (and general manifest variables) a condition that, if satisfied, prevents learning to take place under prior near- ignorance. This condition is shown to be easily satisfied even in the most common statistical problems. We regard these results as a strong form of evidence against the possibility to adopt a condition of prior near-ignorance in real statistical problems.

Published
2011

43. Robust value at risk prediction

Author

Mancini, Loriano, Trojani, Fabio, Mancini, Loriano, and Trojani, Fabio

Abstract

This paper proposes a robust semiparametric bootstrap method to estimate predictive distributions of GARCH-type models. The method is based on a robust estimation of parametric GARCH models and a robustified resampling scheme for GARCH residuals that controls bootstrap instability due to outlying observations. A Monte Carlo simulation shows that our robust method provides more accurate VaR forecasts than classical methods, often by a large extent, especially for several days ahead horizons and/or in presence of outlying observations. An empirical application confirms the simulation results. The robust procedure outperforms in backtesting several other VaR prediction methods, such as RiskMetrics, CAViaR, Historical Simulation, and classical Filtered Historical Simulation methods. We show empirically that robust estimation reduces tail estimation risk, providing more accurate and more stable VaR prediction intervals over time.

Published
2011

44. Multiperiod mean-variance efficient portfolios with endogenous liabilities

Author

Leippold, Markus; https://orcid.org/0000-0001-5983-2360, Trojani, Fabio, Vanini, Paolo, Leippold, Markus; https://orcid.org/0000-0001-5983-2360, Trojani, Fabio, and Vanini, Paolo

Abstract

We study the optimal policies and mean-variance frontiers (MVF) of a multiperiod mean-variance optimization of assets and liabilities (AL). This makes the analysis more challenging than for a setting based on purely exogenous liabilities, in which the optimization is only performed on the assets while keeping liabilities fixed. We show that, under general conditions for the joint AL dynamics, the optimal policies and the MVF can be decomposed into an orthogonal set of basis returns using exterior algebra. This formalism, novel to financial applications, allows us to study analytically the structure of optimal policies and MVF representations under endogenous liabilities in a multidimensional and multiperiod setting. Using a numerical example, we illustrate our methodology by analysing the impact of the rebalancing frequency on the MVF and by highlighting the main differences between exogenous and endogenous liabilities.

Published
2011

45. A general multivariate threshold GARCH model with dynamic conditional correlations

Author

Audrino, Francesco, Trojani, Fabio, Audrino, Francesco, and Trojani, Fabio

Abstract

We introduce a new multivariate GARCH model with multivariate thresholds in conditional correlations and develop a two-step estimation procedure that is feasible in large dimensional applications. Optimal threshold functions are estimated endogenously from the data, and the model conditional covariance matrix is ensured to be positive definite. We study the empirical performance of our model in two applications using US stock and bond market data. The conditional volatility of stock returns exhibits GARCH and threshold structures, but the conditional correlation dynamics depend on piecewise constant thresholds only. We estimate both threshold and GARCH structures in the conditional correlations of stock and government bond returns. In both applications our model has, in terms of statistical and economic significance, higher forecasting power than several other multivariate GARCH models for conditional correlations.

Published
2010

46. Infinitesimal robustness for diffusions

Author

La Vecchia, Davide, Trojani, Fabio, La Vecchia, Davide, and Trojani, Fabio

Abstract

We develop infinitesimally robust statistical procedures for the general diffusion processes. We first prove the existence and uniqueness of the times-series influence function of conditionally unbiased M-estimators for ergodic and stationary diffusions, under weak conditions on the (martingale) estimating function used. We then characterize the robustness of M-estimators for diffusions and derive a class of conditionally unbiased optimal robust estimators. To compute these estimators, we propose a general algorithm, which exploits approximation methods for diffusions in the computation of the robust estimating function. Monte Carlo simulation shows a good performance of our robust estimators and an application to the robust estimation of the exchange rate dynamics within a target zone illustrates the methodology in a real-data application.

Published
2010

47. Ambiguity aversion and the term structure of interest

Author

Gagliardini, Patrick, Porchia, Paolo, Trojani, Fabio, Gagliardini, Patrick, Porchia, Paolo, and Trojani, Fabio

Abstract

This paper studies the term structure implications of a simple structural model in which the representative agent displays ambiguity aversion, modeled by Multiple Priors Recursive Utility. Bond excess returns reflect a premium for ambiguity, which is observationally distinct from the risk premium of affine yield curve models. The ambiguity premium can be large even in the simplest log-utility setting and is also non zero for stochastic factors that have a zero risk premium. A calibrated low-dimensional two-factor model with ambiguity is able to reproduce the deviations from the expectations hypothesis documented in the literature, without modifying in a substantial way the nonlinear mean reversion dynamics of the short interest rate. Moreover, the model does not imply any apparent tradeoff between fitting the first and second moments of the yield curve.

Published
2010

48. Correlation risk and optimal portfolio choice

Author

Buraschi, Andrea, Porchia, Paolo, Trojani, Fabio, Buraschi, Andrea, Porchia, Paolo, and Trojani, Fabio

Abstract

We develop a new framework for multivariate intertemporal portfolio choice that allows us to derive optimal portfolio implications for economies in which the degree of correlation across industries, countries, or asset classes is stochastic. Optimal portfolios include distinct hedging components against both stochastic volatility and correlation risk. We find that the hedging demand is typically larger than in univariate models, and it includes an economically significant covariance hedging component, which tends to increase with the persistence of variance-covariance shocks, the strength of leverage effects, the dimension of the investment opportunity set, and the presence of portfolio constraints.

Published
2010

49. Limits of learning about a categorical latent variable under prior near-ignorance

Author

Piatti, Alberto, Zaffalon, Marco, Trojani, Fabio, Hutter, Marcus, Piatti, Alberto, Zaffalon, Marco, Trojani, Fabio, and Hutter, Marcus

Abstract

In this paper, we consider the coherent theory of (epistemic) uncertainty of Walley, in which beliefs are represented through sets of probability distributions, and we focus on the problem of modeling prior ignorance about a categorical random variable. In this setting, it is a known result that a state of prior ignorance is not compatible with learning. To overcome this problem, another state of beliefs, called near-ignorance, has been proposed. Near-ignorance resembles ignorance very closely, by satisfying some principles that can arguably be regarded as necessary in a state of ignorance, and allows learning to take place. What this paper does, is to provide new and substantial evidence that also near-ignorance cannot be really regarded as a way out of the problem of starting statistical inference in conditions of very weak beliefs. The key to this result is focusing on a setting characterized by a variable of interest that is latent. We argue that such a setting is by far the most common case in practice, and we provide, for the case of categorical latent variables (and general manifest variables) a condition that, if satisfied, prevents learning to take place under prior near-ignorance. This condition is shown to be easily satisfied even in the most common statistical problems. We regard these results as a strong form of evidence against the possibility to adopt a condition of prior near-ignorance in real statistical problems.

Published
2009

50. Limits of learning about a categorical latent variable under prior near-ignorance

Author

Piatti, Alberto, Zaffalon, Marco, Trojani, Fabio, Hutter, Marcus, Piatti, Alberto, Zaffalon, Marco, Trojani, Fabio, and Hutter, Marcus

Abstract

In this paper, we consider the coherent theory of (epistemic) uncertainty of Walley, in which beliefs are represented through sets of probability distributions, and we focus on the problem of modeling prior ignorance about a categorical random variable. In this setting, it is a known result that a state of prior ignorance is not compatible with learning. To overcome this problem, another state of beliefs, called near-ignorance, has been proposed. Near-ignorance resembles ignorance very closely, by satisfying some principles that can arguably be regarded as necessary in a state of ignorance, and allows learning to take place. What this paper does, is to provide new and substantial evidence that also near-ignorance cannot be really regarded as a way out of the problem of starting statistical inference in conditions of very weak beliefs. The key to this result is focusing on a setting characterized by a variable of interest that is latent. We argue that such a setting is by far the most common case in practice, and we provide, for the case of categorical latent variables (and general manifest variables) a condition that, if satisfied, prevents learning to take place under prior near-ignorance. This condition is shown to be easily satisfied even in the most common statistical problems. We regard these results as a strong form of evidence against the possibility to adopt a condition of prior near-ignorance in real statistical problems.

Published
2009

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