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1. Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia

Author

Forte, Dorian, Pellegrino, Roberto Maria, Falvo, Paolo, Garcia-Gonzalez, Paulina, Alabed, Husam B. R., Maltoni, Filippo, Lombardi, Davide, Bruno, Samantha, Barone, Martina, Pasini, Federico, Fabbri, Francesco, Vannini, Ivan, Donati, Benedetta, Cristiano, Gianluca, Sartor, Chiara, Ronzoni, Simona, Ciarrocchi, Alessia, Buratta, Sandra, Urbanelli, Lorena, Emiliani, Carla, Soverini, Simona, Catani, Lucia, Bertolini, Francesco, Argüello, Rafael José, Cavo, Michele, and Curti, Antonio

Published
2024
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3. Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis

Author

Fang, Zijian, Corbizi Fattori, Giuditta, McKerrell, Thomas, Boucher, Rebecca H., Jackson, Aimee, Fletcher, Rachel S., Forte, Dorian, Martin, Jose-Ezequiel, Fox, Sonia, Roberts, James, Glover, Rachel, Harris, Erica, Bridges, Hannah R., Grassi, Luigi, Rodriguez-Meira, Alba, Mead, Adam J., Knapper, Steven, Ewing, Joanne, Butt, Nauman M., Jain, Manish, Francis, Sebastian, Clark, Fiona J., Coppell, Jason, McMullin, Mary F., Wadelin, Frances, Narayanan, Srinivasan, Milojkovic, Dragana, Drummond, Mark W., Sekhar, Mallika, ElDaly, Hesham, Hirst, Judy, Paramor, Maike, Baxter, E. Joanna, Godfrey, Anna L., Harrison, Claire N., and Méndez-Ferrer, Simón

Published
2023
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4. KAT2A complexes ATAC and SAGA play unique roles in cell maintenance and identity in hematopoiesis and leukemia

Author

Arede, Liliana, Foerner, Elena, Wind, Selinde, Kulkarni, Rashmi, Domingues, Ana Filipa, Giotopoulos, George, Kleinwaechter, Svenja, Mollenhauer-Starkl, Maximilian, Davison, Holly, Chandru, Aditya, Asby, Ryan, Samarista, Ralph, Gupta, Shikha, Forte, Dorian, Curti, Antonio, Scheer, Elisabeth, Huntly, Brian J.P., Tora, Laszlo, and Pina, Cristina

Published
2022
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5. Tracking Response and Resistance in Acute Myeloid Leukemia through Single-Cell DNA Sequencing Helps Uncover New Therapeutic Targets.

Author

Bruno, Samantha, Borsi, Enrica, Patuelli, Agnese, Bandini, Lorenza, Mancini, Manuela, Forte, Dorian, Nanni, Jacopo, Barone, Martina, Grassi, Alessandra, Cristiano, Gianluca, Venturi, Claudia, Robustelli, Valentina, Atzeni, Giulia, Mosca, Cristina, De Santis, Sara, Monaldi, Cecilia, Poletti, Andrea, Terragna, Carolina, Curti, Antonio, and Cavo, Michele

Subjects
ACUTE myeloid leukemia, PROTEIN-tyrosine kinase inhibitors, DRUG resistance, DNA sequencing, NATURAL immunity
Abstract

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the FLT3 gene represent the most frequent mutations identified at diagnosis. The development of tyrosine kinase inhibitors (TKIs) has improved the clinical outcomes of FLT3-mutated patients (Pt). However, overcoming resistance to these drugs remains a challenge. To unravel the molecular mechanisms underlying therapy resistance and clonal selection, we conducted a longitudinal analysis using a single-cell DNA sequencing approach (MissionBioTapestri® platform, San Francisco, CA, USA) in two patients with FLT3-mutated AML. To this end, samples were collected at the time of diagnosis, during TKI therapy, and at relapse or complete remission. For Pt #1, disease resistance was associated with clonal expansion of minor clones, and 2nd line TKI therapy with gilteritinib provided a proliferative advantage to the clones carrying NRAS and KIT mutations, thereby responsible for relapse. In Pt #2, clonal architecture was less complex, and 1st line TKI therapy with midostaurin was able to eradicate the leukemic clones. Our results corroborate previous findings about clonal selection driven by TKIs, highlighting the importance of a deeper characterization of individual clonal architectures for choosing the best treatment plan for personalized approaches aimed at optimizing outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy

Author

Forte, Dorian, García-Fernández, María, Sánchez-Aguilera, Abel, Stavropoulou, Vaia, Fielding, Claire, Martín-Pérez, Daniel, López, Juan Antonio, Costa, Ana S.H., Tronci, Laura, Nikitopoulou, Efterpi, Barber, Michael, Gallipoli, Paolo, Marando, Ludovica, Fernández de Castillejo, Carlos López, Tzankov, Alexandar, Dietmann, Sabine, Cavo, Michele, Catani, Lucia, Curti, Antonio, Vázquez, Jesús, Frezza, Christian, Huntly, Brian J., Schwaller, Juerg, and Méndez-Ferrer, Simón

Published
2020
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7. Distinct profile of CD34+ cells and plasma-derived extracellular vesicles from triple-negative patients with Myelofibrosis reveals potential markers of aggressive disease

Author

Forte, Dorian, Barone, Martina, Morsiani, Cristina, Simonetti, Giorgia, Fabbri, Francesco, Bruno, Samantha, Bandini, Erika, Sollazzo, Daria, Collura, Salvatore, Deregibus, Maria Chiara, Auteri, Giuseppe, Ottaviani, Emanuela, Vianelli, Nicola, Camussi, Giovanni, Franceschi, Claudio, Capri, Miriam, Palandri, Francesca, Cavo, Michele, and Catani, Lucia

Published
2021
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8. Ex vivo characterization of acute myeloid leukemia patients undergoing hypomethylating agents and venetoclax regimen reveals a venetoclax-specific effect on non-suppressive regulatory T cells and bona fide PD-1+TIM3+ exhausted CD8+ T cells.

Author

Corradi, Giulia, Forte, Dorian, Cristiano, Gianluca, Polimeno, Andrea, Ciciarello, Marilena, Salvestrini, Valentina, Bandini, Lorenza, Robustelli, Valentina, Ottaviani, Emanuela, Cavo, Michele, Ocadlikova, Darina, and Curti, Antonio

Subjects
REGULATORY T cells, CYTARABINE, ACUTE myeloid leukemia, VENETOCLAX, IMMUNOTHERAPY, T cells, IMMUNE checkpoint proteins
Abstract

Acute myeloid leukemia (AML) is an aggressive heterogeneous disease characterized by several alterations of the immune system prompting disease progression and treatment response. The therapies available for AML can affect lymphocyte function, limiting the efficacy of immunotherapy while hindering leukemia-specific immune reactions. Recently, the treatment based on Venetoclax (VEN), a specific B-cell lymphoma 2 (BCL-2) inhibitor, in combination with hypomethylating agents (HMAs) or low-dose cytarabine, has emerged as a promising clinical strategy in AML. To better understand the immunological effect of VEN treatment, we characterized the phenotype and immune checkpoint (IC) receptors' expression on CD4+ and CD8+ T cells from AML patients after the first and second cycle of HMA in combination with VEN. HMA and VEN treatment significantly increased the percentage of naive CD8+ T cells and TIM-3+ CD4+ and CD8+ T cells and reduced cytokine-secreting non-suppressive T regulatory cells (Tregs). Of note, a comparison between AML patients treated with HMA only and HMA in combination with VEN revealed the specific contribution of VEN in modulating the immune cell repertoire. Indeed, the reduction of cytokine-secreting non-suppressive Tregs, the increased TIM-3 expression on CD8+ T cells, and the reduced co-expression of PD-1 and TIM-3 on both CD4+ and CD8+ T cells are all VEN-specific. Collectively, our study shed light on immune modulation induced by VEN treatment, providing the rationale for a novel therapeutic combination of VEN and IC inhibitors in AML patients. [ABSTRACT FROM AUTHOR]

Published
2024
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9. PB1865: NPM1-MUT MONITORING DURING GILTERITINIB TREATMENT IDENTIFIES DIFFERENT DYNAMICAL PATTERNS IN RESPONSIVE PATIENTS

Author

Sartor, Chiara, primary, Ottaviani, Emanuela, additional, Nanni, Jacopo, additional, Ciruolo, Raffaele, additional, Cristiano, Gianluca, additional, Zannoni, Letizia, additional, Zingarelli, Federico, additional, Bandini, Lorenza, additional, Patuelli, Agnese, additional, Venturi, Claudia, additional, Robustellu, Valentina, additional, Forte, Dorian, additional, Cavo, Michele, additional, Curti, Antonio, additional, and Papayannidis, Cristina, additional

Published
2023
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11. Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability

Author

Forte, Dorian, primary, Pellegrino, Roberto Maria, additional, Trabanelli, Sara, additional, Tonetti, Tommaso, additional, Ricci, Francesca, additional, Cenerenti, Mara, additional, Comai, Giorgia, additional, Tazzari, Pierluigi, additional, Lazzarotto, Tiziana, additional, Buratta, Sandra, additional, Urbanelli, Lorena, additional, Narimanfar, Ghazal, additional, Alabed, Husam B. R., additional, Mecucci, Cristina, additional, La Manna, Gaetano, additional, Emiliani, Carla, additional, Jandus, Camilla, additional, Ranieri, Vito Marco, additional, Cavo, Michele, additional, Catani, Lucia, additional, and Palandri, Francesca, additional

Published
2023
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12. Tamoxifen reduces mitochondrial respiration, oncogenic signaling and mutant allele burden in a myeloproliferative neoplasm subset

Author

Fang, Zijian, primary, Fattori, Giuditta, additional, McKerrell, Thomas, additional, Boucher, Rebecca, additional, Jackson, Aimee, additional, Fletcher, Rachel, additional, Forte, Dorian, additional, Martin, Jose-Ezequiel, additional, Fox, Sonia, additional, Roberts, James, additional, Glover, Rachel, additional, Harris, Erica, additional, Bridges, Hannah, additional, Grassi, Luigi, additional, Rodriguez-Meira, Alba, additional, Mead, Adam, additional, Knapper, Steven, additional, Ewing, Joanne, additional, Butt, Nauman, additional, Jain, Manish, additional, Francis, Sebastian, additional, Clark, Fiona, additional, Coppell, Jason, additional, McMullin, Mary, additional, Wadelin, Frances, additional, Narayanan, Srinivasan, additional, Milojkovic, Dragana, additional, Drummond, Mark, additional, Sekhar, Mallika, additional, ElDaly, Hesham, additional, Hirst, Judy, additional, Paramor, Maike, additional, Baxter, Elizabeth, additional, Godfrey, Anna, additional, Harrison, Claire, additional, and Mendez-Ferrer, Simon, additional

Published
2023
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14. Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability

Author

Forte, Dorian, Pellegrino, Roberto Maria, Trabanelli, Sara, Tonetti, Tommaso, Ricci, Francesca, Cenerenti, Mara, Comai, Giorgia, Tazzari, Pierluigi, Lazzarotto, Tiziana, Buratta, Sandra, Urbanelli, Lorena, Narimanfar, Ghazal, Alabed, Husam B. R., Mecucci, Cristina, La Manna, Gaetano, Emiliani, Carla, Jandus, Camilla, Ranieri, Vito Marco, Cavo, Michele, Catani, Lucia, Palandri, Francesca, Forte D., Pellegrino R.M., Trabanelli S., Tonetti T., Ricci F., Cenerenti M., Comai G., Tazzari P., Lazzarotto T., Buratta S., Urbanelli L., Narimanfar G., Alabed H.B.R., Mecucci C., La Manna G., Emiliani C., Jandus C., Ranieri V.M., Cavo M., Catani L., and Palandri F.

Subjects
SARS-CoV-2, lipidomic, Immunology, innate lymphoid cell, innate lymphoid cells, Immunology and Allergy, COVID-19, extracellular vesicles and particles, type 2 innate lymphoid cell, extracellular vesicles and particle
Abstract

IntroductionExtracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score.MethodsPeripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs.ResultsWe observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs.DiscussionIn summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis.

Published
2023

15. Extracellular Vesicle-Based Liquid Biopsy Shows Clinical Relevance and Reveals Links with Single-Cell Metabolic Signature in Acute Myeloid Leukemia

Author

Forte, Dorian, primary, Argüello, Rafael J., additional, Pellegrino, Roberto Maria, additional, Alabed, Husam B.R., additional, Barone, Martina, additional, Bruno, Samantha, additional, Fabbri, Francesco, additional, Vannini, Ivan, additional, Cristiano, Gianluca, additional, Buratta, Sandra, additional, Urbanelli, Lorena, additional, Emiliani, Carla, additional, Cavo, Michele, additional, and Curti, Antonio, additional

Published
2022
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16. Critical Role of Hodgkin Lymphoma Cells-Derived Large and Small Extracellular Vesicles in the Regulation of the Immune-Inflammatory Microenvironment

Author

Maltoni, Filippo, primary, Ciardiello, Chiara, additional, Nanni, Laura, additional, Barone, Martina, additional, Narimanfar, Ghazal, additional, Casadei, Beatrice, additional, Argnani, Lisa, additional, Broccoli, Alessandro, additional, Forte, Dorian, additional, Budillon, Alfredo, additional, Zinzani, Pier Luigi, additional, and Catani, Lucia, additional

Published
2022
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20. Circulating Extracellular Vesicles from Acute Myeloid Leukemia Patients Drive Distinct Metabolic Profile of Leukemic Cells and Reveal Crucial Lipidomic Biomarkers

Author

Forte, Dorian, primary, Pellegrino, Roberto Maria, additional, Fabbri, Francesco, additional, Vannini, Ivan, additional, Bruno, Samantha, additional, Corradi, Giulia, additional, Argüello, Rafael J., additional, Cristiano, Gianluca, additional, Buratta, Sandra, additional, Urbanelli, Lorena, additional, Emiliani, Carla, additional, Cavo, Michele, additional, and Curti, Antonio, additional

Published
2021
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22. Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia

Author

Bruno, Samantha, primary, Bandini, Lorenza, additional, Patuelli, Agnese, additional, Robustelli, Valentina, additional, Venturi, Claudia, additional, Mancini, Manuela, additional, Forte, Dorian, additional, De Santis, Sara, additional, Monaldi, Cecilia, additional, Grassi, Alessandra, additional, Chiurumbolo, Gabriella, additional, Paolini, Stefania, additional, Cristiano, Gianluca, additional, Papayannidis, Cristina, additional, Sartor, Chiara, additional, Nanni, Jacopo, additional, Ottaviani, Emanuela, additional, Curti, Antonio, additional, Cavo, Michele, additional, and Soverini, Simona, additional

Published
2021
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23. Additional file 1 of Distinct profile of CD34+ cells and plasma-derived extracellular vesicles from triple-negative patients with Myelofibrosis reveals potential markers of aggressive disease

Author

Forte, Dorian, Barone, Martina, Morsiani, Cristina, Simonetti, Giorgia, Fabbri, Francesco, Bruno, Samantha, Bandini, Erika, Sollazzo, Daria, Collura, Salvatore, Deregibus, Maria Chiara, Auteri, Giuseppe, Ottaviani, Emanuela, Vianelli, Nicola, Camussi, Giovanni, Franceschi, Claudio, Capri, Miriam, Palandri, Francesca, Cavo, Michele, and Catani, Lucia

Subjects
sense organs
Abstract

Additional file 1: Table S1. Characteristics of the patient population. Table S2. Differentially expressed transcripts. Table S3. List of the selected miRNAs with their relative fold-changes (FC). Figure S1. Characterization by TME and NTA of EVs. Figure S2. EV characterization by flow cytometry. Figure S3. Representative western blot and quantification graph for TOMM20.

Published
2021
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25. Corrigendum: Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells

Author

Salvestrini, Valentina, primary, Ciciarello, Marilena, additional, Pensato, Valentina, additional, Simonetti, Giorgia, additional, Laginestra, Maria Antonella, additional, Bruno, Samantha, additional, Pazzaglia, Martina, additional, De Marchi, Elena, additional, Forte, Dorian, additional, Orecchioni, Stefania, additional, Martinelli, Giovanni, additional, Bertolini, Francesco, additional, Méndez-Ferrer, Simon, additional, Adinolfi, Elena, additional, Di Virgilio, Francesco, additional, Cavo, Michele, additional, and Curti, Antonio, additional

Published
2021
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27. Abstract 4946: Bitter taste receptors system is expressed and functional in both HSCs and leukemic cells

Author

Salvestrini, Valentina, primary, Pensato, Valentina, additional, Ciciarello, Marilena, additional, Simonetti, Giorgia, additional, Bruno, Samantha, additional, Pazzaglia, Martina, additional, De Marchi, Elena, additional, Forte, Dorian, additional, Orecchioni, Stefania, additional, Martinelli, Giovanni, additional, Bertolini, Francesco, additional, Mendez-Ferrer, Simon, additional, Adinolfi, Elena, additional, Cavo, Michele, additional, and Curti, Antonio, additional

Published
2020
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28. Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells

Author

Salvestrini, Valentina, primary, Ciciarello, Marilena, additional, Pensato, Valentina, additional, Simonetti, Giorgia, additional, Laginestra, Maria Antonella, additional, Bruno, Samantha, additional, Pazzaglia, Martina, additional, De Marchi, Elena, additional, Forte, Dorian, additional, Orecchioni, Stefania, additional, Martinelli, Giovanni, additional, Bertolini, Francesco, additional, Méndez-Ferrer, Simon, additional, Adinolfi, Elena, additional, Di Virgilio, Francesco, additional, Cavo, Michele, additional, and Curti, Antonio, additional

Published
2020
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29. Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms

Author

Forte, Dorian, primary, Fanelli, Flaminia, additional, Mezzullo, Marco, additional, Barone, Martina, additional, Corradi, Giulia, additional, Auteri, Giuseppe, additional, Bartoletti, Daniela, additional, Martello, Marina, additional, Ottaviani, Emanuela, additional, Terragna, Carolina, additional, Curti, Antonio, additional, Pagotto, Uberto, additional, Palandri, Francesca, additional, Cavo, Michele, additional, and Catani, Lucia, additional

Published
2020
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30. Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: Real‐world data

Author

Palandri, Francesca, primary, Breccia, Massimo, additional, Tiribelli, Mario, additional, Bonifacio, Massimiliano, additional, Benevolo, Giulia, additional, Iurlo, Alessandra, additional, Elli, Elena M., additional, Binotto, Gianni, additional, Tieghi, Alessia, additional, Polverelli, Nicola, additional, Martino, Bruno, additional, Abruzzese, Elisabetta, additional, Bergamaschi, Micaela, additional, Heidel, Florian H., additional, Cavazzini, Francesco, additional, Crugnola, Monica, additional, Bosi, Costanza, additional, Isidori, Alessandro, additional, Auteri, Giuseppe, additional, Forte, Dorian, additional, Latagliata, Roberto, additional, Griguolo, Davide, additional, Cattaneo, Daniele, additional, Trawinska, Malgorzata, additional, Bartoletti, Daniela, additional, Krampera, Mauro, additional, Semenzato, Gianpietro, additional, Lemoli, Roberto M., additional, Cuneo, Antonio, additional, Di Raimondo, Francesco, additional, Vianelli, Nicola, additional, Cavo, Michele, additional, and Palumbo, Giuseppe A., additional

Published
2020
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31. The role of circulating monocytes and JAK inhibition in the infectious-driven inflammatory response of myelofibrosis

Author

Barone, Martina, primary, Catani, Lucia, additional, Ricci, Francesca, additional, Romano, Marco, additional, Forte, Dorian, additional, Auteri, Giuseppe, additional, Bartoletti, Daniela, additional, Ottaviani, Emanuela, additional, Tazzari, Pier Luigi, additional, Vianelli, Nicola, additional, Cavo, Michele, additional, and Palandri, Francesca, additional

Published
2020
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32. The Infection-Driven Production/Secretion of Inflammatory Cytokines By Circulating Monocytes of Myelofibrosis Is Defective and Is Reactivated after In VivoJAK1/2 Inhibition

Author

Barone, Martina, primary, Ricci, Francesca, additional, Romano, Marco, additional, Forte, Dorian, additional, Auteri, Giuseppe, additional, Fabbri, Francesco, additional, Ottaviani, Emanuela, additional, Tazzari, Pierluigi, additional, Vianelli, Nicola, additional, Martinelli, Giovanni, additional, Cavo, Michele, additional, Palandri, Francesca, additional, and Catani, Lucia, additional

Published
2019
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34. Circulating Platelet Vs Megakaryocyte-Derived Microparticles Identify Myelofibrosis Patients with JAK2V617F Mutation, High Disease Burden and Ruxolitinib Response

Author

Forte, Dorian, Barone, Martina, Ricci, Francesca, Sollazzo, Daria, Romano, Marco, Ottaviani, Emanuela, Auteri, Giuseppe, Vianelli, Nicola, Martinelli, Giovanni, Cavo, Michele, Tazzari, Pierluigi, FRANCESCA PALANDRI, Catani, Lucia, and Forte Dorian, Barone Martina, Ricci Francesca, Sollazzo Daria, Romano Marco, Ottaviani Emanuela, Auteri Giuseppe, Vianelli Nicola, Martinelli Giovanni, Cavo Michele, Tazzari Pierluigi, Palandri Francesca, Catani Lucia

Subjects
Megakaryocyte, Myelofibrosis, Platelet microparticles, Ruxolitinib
Abstract

Myelofibrosis (MF) is a clonal neoplasia of the hematopoietic stem/progenitor cells characterized by distinctive abnormalities in megakaryocyte (MK) development and platelet (PLT) activation. Therapy with Ruxolitinib (RUX), a JAK1/2 inhibitor, suppresses both clonal myeloproliferation and release of proinflammatory cytokines, reducing splenomegaly and constitutional symptoms in around half of patients (pts). However, a deeply understanding of the activated inflammatory pathways and the biological effects of RUX is still lacking. Microparticles (MPs) produced by cells may occur as a key cellular communication process in homeostasis, which may increase under inflammatory stimuli and neoplastic diseases. Most of circulating MPs are of PLT and MK origin. Their role and modulation in the inflammatory microenvironment of MF are elusive. We evaluated whether circulating MK and PLT-derived MPs are dysregulated in MF and how the inflammatory microenvironment may drive their pattern. Also, we investigated whether circulating MK and PLT-derived MPs may be considered as a novel biomarker of response to RUX. EDTA-anticoagulated peripheral blood (PB) was collected from 42 MF pts, 13 Polycythemia Vera (PV)/Essential Thrombocythemia (ET) pts and 10 age/sex-matched healthy donors (HD). Samples from MF, ET/PV pts were obtained at diagnosis or out of cytotoxic treatment for at least 3 months; 14 MF pts were studied also after 6 months of RUX therapy. Spleen response (SR) was evaluated according to the 2013 IWG-MRT criteria. PLT (CD61+CD62P+) and MK (CD61+CD62P-)-derived MPs were analysed in PLT poor plasma samples by flow cytometry (CytoFLEX, Beckman Coulter, MPs ranging 0.5-0.9 μm). MF pts were JAK2V617F (n=24), CALR (n=9) and MPL (n=4) mutated; 5 pts were TN. The mean percentage of PLT-derived MPs of JAK2V617F mutated pts was significantly increased as compared with HD (p

Published
2017

35. The Malignant Hemopoietic Clone of Triple Negative Patients with Myelofibrosis Shows in Vitro Functional Defects but Is Highly Responsive to the Pro-Survival Signals of Circulating Autologous Microvesicles

Author

Catani, Lucia, primary, Sollazzo, Daria, additional, Forte, Dorian, additional, Barone, Martina, additional, Morsiani, Cristina, additional, Fabbri, Francesco, additional, Simonetti, Giorgia, additional, Ricci, Francesca, additional, Bruno, Samantha, additional, Calonghi, Natalia, additional, Ottaviani, Emanuela, additional, Romano, Marco, additional, Tazzari, Pierluigi, additional, Franceschi, Claudio, additional, Bonafè, Massimiliano, additional, Vianelli, Nicola, additional, Martinelli, Giovanni, additional, Cavo, Michele, additional, Capri, Miriam, additional, Auteri, Giuseppe, additional, and Palandri, Francesca, additional

Published
2018
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37. Circulating megakaryocyte and platelet microvesicles correlate with response to ruxolitinib and distinct disease severity in patients with myelofibrosis

Author

Barone, Martina, primary, Ricci, Francesca, additional, Sollazzo, Daria, additional, Ottaviani, Emanuela, additional, Romano, Marco, additional, Auteri, Giuseppe, additional, Bartoletti, Daniela, additional, Reggiani, Maria L. B., additional, Vianelli, Nicola, additional, Tazzari, Pier L., additional, Cavo, Michele, additional, Forte, Dorian, additional, Palandri, Francesca, additional, and Catani, Lucia, additional

Published
2018
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38. Mobilized Peripheral Blood versus Cord Blood: Insight into the Distinct Role of Proinflammatory Cytokines on Survival, Clonogenic Ability, and Migration of CD34+Cells

Author

Forte, Dorian, primary, Sollazzo, Daria, additional, Barone, Martina, additional, Allegri, Marisole, additional, di Martella Orsi, Angela, additional, Romano, Marco, additional, Sinigaglia, Barbara, additional, Auteri, Giuseppe, additional, Vianelli, Nicola, additional, Cavo, Michele, additional, Palandri, Francesca, additional, and Catani, Lucia, additional

Published
2018
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39. Leukemic Stem/Progenitor Cells and their Microenvironment: The Role of Crucial Inflammatory Factors and Bone Marrow-Derived Mesenspheres

Author

Forte, Dorian

Subjects
hemic and lymphatic diseases, MED/15 Malattie del sangue
Abstract

In this thesis, we aimed to investigate the role of inflammation in Myelofibrosis (MF) and the cross-talk between leukemic cells and their microenvironment in Acute Myeloid Leukemia (AML). In MF, we explored how inflammatory stimuli could modulate the malignant clone of HSCs. We observed potent effects of combinations of pro-inflammatory cytokines (IL-1β/ TNF-α/TIMP-1) on survival, clonogenic potential and migration of CD34+ cells isolated from MF patients at diagnosis or without treatment. Our data suggest that the malignant clone is driven not only by intrinsic properties but also by the interplay with the inflammatory microenvironment. In AML, we showed that an inhibitor of metalloproteinases (TIMP-1) could be considered as a ‘bad actor’ in the leukemic context. TIMP-1 modulates different pathways and we highlighted a cytokine function on AML blasts from AML patients at diagnosis. The survival, migration and proliferation of AML blasts was supported by TIMP-1, delineating a signaling pathway mediated through its receptor CD63 and PI3K/Akt/p21. In parallel, in a mouse model of AML MLL-AF9, we also explored the interaction between bone marrow stromal cells (BMSCs) and leukemic blasts. Through a novel system of co-cultures, we demonstrated the supportive/protective role of BMSCs, as non-adherent cells 'mesenspheres'. In this cross-talk we found a reduction of ROS levels and lipid peroxidation in leukemic blasts co-cultured with BMSCs, in stressed conditions. Importantly, we found also chemo-protective role of mesenspheres on leukemic cells mediated by mitochondria transfer. Surprisingly, this interaction could be explained as transfer of sources of anti-oxidants and nutrients between BMSCs and leukemic cells. Through the entire work, we shed new light on mechanisms and networks in haematological malignancies, such as MF and AML, driving toward novel therapeutic strategy to switch off an inflammatory microenvironment and key players of the malignant niches.

Published
2017
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42. Mutations in JAK2 and Calreticulin genes are associated with specific alterations of the immune system in myelofibrosis

Author

Romano, Marco, primary, Sollazzo, Daria, additional, Trabanelli, Sara, additional, Barone, Martina, additional, Polverelli, Nicola, additional, Perricone, Margherita, additional, Forte, Dorian, additional, Luatti, Simona, additional, Cavo, Michele, additional, Vianelli, Nicola, additional, Jandus, Camilla, additional, Palandri, Francesca, additional, and Catani, Lucia, additional

Published
2017
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43. The relevance of a low JAK2V617F allele burden in clinical practice: a monocentric study

Author

Perricone, Margherita, primary, Polverelli, Nicola, additional, Martinelli, Giovanni, additional, Catani, Lucia, additional, Ottaviani, Emanuela, additional, Zuffa, Elisa, additional, Franchini, Eugenia, additional, Dizdari, Arbana, additional, Forte, Dorian, additional, Sabattini, Elena, additional, Cavo, Michele, additional, Vianelli, Nicola, additional, and Palandri, Francesca, additional

Published
2017
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44. Circulating megakaryocyte and platelet microvesicles correlate with response to ruxolitinib and distinct disease severity in patients with myelofibrosis.

Author

Barone, Martina, Ricci, Francesca, Sollazzo, Daria, Ottaviani, Emanuela, Romano, Marco, Auteri, Giuseppe, Bartoletti, Daniela, Reggiani, Maria L. B., Vianelli, Nicola, Tazzari, Pier L., Cavo, Michele, Forte, Dorian, Palandri, Francesca, and Catani, Lucia

Subjects
MYELOFIBROSIS, BLOOD platelet activation, PLATELET count
Abstract

The article focuses on a study which aims to investigate the profile of microvesicles (MV) in myelofibrosis (MF) and essential thrombocythaemia (ET) whether MV proportions could be related to severity of MF as well as the role of inflammation on MV frequency in MF. Information about the effects of ruxolitinib on MVs in MF and the frequency of circulating megakaryocyte- and platelet-MVs is presented.

Published
2019
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47. Additional file 3: Table S3. of Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohnâ s disease patients in a mouse model of colitis

Author

Forte, Dorian, Ciciarello, Marilena, Valerii, Maria, Fazio, Luigia De, Cavazza, Elena, Giordano, Rosaria, Parazzi, Valentina, Lazzari, Lorenza, Laureti, Silvio, Rizzello, Fernando, Cavo, Michele, Curti, Antonio, Lemoli, Roberto, Spisni, Enzo, and Catani, Lucia

Abstract

Presenting histological damage score criteria. Summary of the criteria used to assign the scores added to determine the histological damage score. (DOC 31 kb)

Published
2015
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48. Additional file 4: Figure S1. of Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn’s disease patients in a mouse model of colitis

Author

Forte, Dorian, Ciciarello, Marilena, Valerii, Maria, Fazio, Luigia De, Cavazza, Elena, Giordano, Rosaria, Parazzi, Valentina, Lazzari, Lorenza, Laureti, Silvio, Rizzello, Fernando, Cavo, Michele, Curti, Antonio, Lemoli, Roberto, Spisni, Enzo, and Catani, Lucia

Abstract

Showing that Nile Red-labeled adCD-MSCs are viable and maintain phenotypic and differentiative properties as compared with unlabelled cells. Proliferation rate (cell titer assay), immunophenotype (flow cytometry), and differentiation potential (Alizarin red and Oil red O staining) of Nile Red-labeled adCD-MSCs (adCD-MSCs+NR) compared with unlabeled adCD-MSCs. Nile Red-labeled adCD-MSCs are viable and maintain phenotypic and differentiative properties compared with unlabeled cells. a Proliferation rate is evaluated by cell titer assay and expressed as fold-change taking the value of unlabeled cells at each time point as 1. Data expressed as mean ± SEM of at least three experiments. All differences are not significant (p value not significant). NR Nile Red. b Flow cytometric immunophenotype of Nile Red-labeled adCD-MSCs (adCD-MSCs+NR) is similar to that of unlabeled adCD-MSCs. Data expressed as mean ± SEM of at least two experiments. All differences are not significant (p value not significant). As a proof of differentiation potential, osteogenic and adipogenic process are shown. Alizarin red and Oil red O staining of unlabeled c, d and Nile Red-labeled e, f adCD-MSCs cultured for 3 weeks in osteogenic c, e and adipogenic conditions d, f. Magnification 20×; scale bar, 100 μm. (PDF 1843 kb)

Published
2015
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49. Additional file 2: Table S2. of Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohnâ s disease patients in a mouse model of colitis

Author

Forte, Dorian, Ciciarello, Marilena, Valerii, Maria, Fazio, Luigia De, Cavazza, Elena, Giordano, Rosaria, Parazzi, Valentina, Lazzari, Lorenza, Laureti, Silvio, Rizzello, Fernando, Cavo, Michele, Curti, Antonio, Lemoli, Roberto, Spisni, Enzo, and Catani, Lucia

Abstract

Presenting DAI score criteria. Summary of the criteria used to assign the scores added to determine the DAI in mice daily. (DOCX 13 kb)

Published
2015
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50. Additional file 1: Table S1. of Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohnâ s disease patients in a mouse model of colitis

Author

Forte, Dorian, Ciciarello, Marilena, Valerii, Maria, Fazio, Luigia De, Cavazza, Elena, Giordano, Rosaria, Parazzi, Valentina, Lazzari, Lorenza, Laureti, Silvio, Rizzello, Fernando, Cavo, Michele, Curti, Antonio, Lemoli, Roberto, Spisni, Enzo, and Catani, Lucia

Abstract

Presenting sample demographics. Summary of the main features of CD patients from which adCD-MSCs were isolated. Data for healthy donors from which adHD-MSCs were isolated for the comparison of biological properties are also shown. (DOC 34 kb)

Published
2015
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