15 results on '"Salvatore Nicola Bertuccio"'
Search Results
2. Neuronopathic Gaucher disease models reveal defects in cell growth promoted by Hippo pathway activation
- Author
-
Daria Messelodi, Silvia Strocchi, Salvatore Nicola Bertuccio, Pascale Baden, Valentina Indio, Federico M. Giorgi, Alberto Taddia, Salvatore Serravalle, Sabrina Valente, Alessio di Fonzo, Emanuele Frattini, Roberto Bernardoni, Annalisa Pession, Daniela Grifoni, Michela Deleidi, Annalisa Astolfi, and Andrea Pession
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Abstract Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD.
- Published
- 2023
- Full Text
- View/download PDF
3. P405: IN VITRO RESPONSE TO BCL-2 INHIBITION IN PEDIATRIC B PRECURSOR ALL WITH HIGH RISK CYTOGENETICS
- Author
-
Francesca Gottardi, Daria Messelodi, Domenico D’amico, Francesco Baccelli, Davide Leardini, Salvatore Nicola Bertuccio, and Riccardo Masetti
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
- Full Text
- View/download PDF
4. Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants
- Author
-
Francesco Baccelli, Davide Leardini, Edoardo Muratore, Daria Messelodi, Salvatore Nicola Bertuccio, Maria Chiriaco, Caterina Cancrini, Francesca Conti, Fausto Castagnetti, Lucia Pedace, Andrea Pession, Ayami Yoshimi, Charlotte Niemeyer, Marco Tartaglia, Franco Locatelli, and Riccardo Masetti
- Subjects
CBL ,JMML ,Immune dysregulation ,CBL syndrome ,SH2B3 ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background CBL syndrome is a RASopathy caused by heterozygous germline mutations of the Casitas B-lineage lymphoma (CBL) gene. It is characterized by heterogeneous clinical phenotype, including developmental delay, facial dysmorphisms, cardiovascular malformations and an increased risk of cancer development, particularly juvenile myelomonocytic leukemia (JMML). Although the clinical phenotype has been progressively defined in recent years, immunological manifestations have not been well elucidated to date. Methods We studied the genetic, immunological, coagulative, and clinical profile of a family with CBL syndrome that came to our observation after the diagnosis of JMML, with homozygous CBL mutation, in one of the members. Results Variant analysis revealed the co-occurrence of CBL heterozygous mutation (c.1141 T > C) and SH2B3 mutation (c.1697G > A) in two other members. Patients carrying both mutations showed an ALPS-like phenotype characterized by lymphoproliferation, cytopenia, increased double-negative T-cells, impaired Fas-mediated lymphocyte apoptosis, altered cell death in PBMC and low TRECs expression. A coagulative work-up was also performed and showed the presence of subclinical coagulative alterations in patients carrying both mutations. Conclusion In the reported family, we described immune dysregulation, as part of the clinical spectrum of CBL mutation with the co-occurrence of SH2B3.
- Published
- 2022
- Full Text
- View/download PDF
5. Peripheral blood cellular profile at pre-lymphodepletion is associated with CD19-targeted CAR-T cell-associated neurotoxicity
- Author
-
Serena De Matteis, Michele Dicataldo, Beatrice Casadei, Gianluca Storci, Noemi Laprovitera, Mario Arpinati, Enrico Maffini, Pietro Cortelli, Maria Guarino, Francesca Vaglio, Maria Naddeo, Barbara Sinigaglia, Luca Zazzeroni, Serafina Guadagnuolo, Enrica Tomassini, Salvatore Nicola Bertuccio, Daria Messelodi, Manuela Ferracin, Massimiliano Bonafè, Pier Luigi Zinzani, and Francesca Bonifazi
- Subjects
chimeric antigen receptor ,senescence ,inflammation ,neurotoxicity ,myeloid activation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundInfusion of second generation autologous CD19-targeted chimeric antigen receptor (CAR) T cells in patients with R/R relapsed/refractory B-cell lymphoma (BCL) is affected by inflammatory complications, such as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Current literature suggests that the immune profile prior to CAR-T infusion modifies the chance to develop ICANS.MethodsThis is a monocenter prospective study on 53 patients receiving approved CAR T-cell products (29 axi-cel, 24 tisa-cel) for R/R-BCL. Clinical, biochemical, and hematological variables were analyzed at the time of pre-lymphodepletion (pre-LD). In a subset of 21 patients whose fresh peripheral blood sample was available, we performed cytofluorimetric analysis of leukocytes and extracellular vesicles (EVs). Moreover, we assessed a panel of soluble plasma biomarkers (IL-6/IL-10/GDF-15/IL-15/CXCL9/NfL) and microRNAs (miR-146a-5p, miR-21-5p, miR-126-3p, miR-150-5p) which are associated with senescence and inflammation.ResultsMultivariate analysis at the pre-LD time-point in the entire cohort (n=53) showed that a lower percentage of CD3+CD8+ lymphocytes (38.6% vs 46.8%, OR=0.937 [95% CI: 0.882-0.996], p=0.035) and higher levels of serum C-reactive protein (CRP, 4.52 mg/dl vs 1.00 mg/dl, OR=7.133 [95% CI: 1.796-28], p=0.005) are associated with ICANS. In the pre-LD samples of 21 patients, a significant increase in the percentage of CD8+CD45RA+CD57+ senescent cells (median % value: 16.50% vs 9.10%, p=0.009) and monocytic-myeloid derived suppressor cells (M-MDSC, median % value: 4.4 vs 1.8, p=0.020) was found in ICANS patients. These latter also showed increased levels of EVs carrying CD14+ and CD45+ myeloid markers, of the myeloid chemokine CXCL-9, as well of the MDSC-secreted cytokine IL-10. Notably, the serum levels of circulating neurofilament light chain, a marker of neuroaxonal injury, were positively correlated with the levels of senescent CD8+ T cells, M-MDSC, IL-10 and CXCL-9. No variation in the levels of the selected miRNAs was observed between ICANS and no-ICANS patients.DiscussionOur data support the notion that pre-CAR-T systemic inflammation is associated with ICANS. Higher proportion of senescence CD8+ T cells and M-MDSC correlate with early signs of neuroaxonal injury at pre-LD time-point, suggesting that ICANS may be the final event of a process that begins before CAR-T infusion, consequence to patient clinical history.
- Published
- 2023
- Full Text
- View/download PDF
6. Case report: Senescence as mechanism of resistance to Pembrolizumab in a Lymphoma patient who failed CD19-Targeted CAR-T cell therapy
- Author
-
Serena De Matteis, Beatrice Casadei, Ginevra Lolli, Michele Dicataldo, Francesco Barbato, Elisa Dan, Andrea Paccagnella, Barbara Sinigaglia, Clara Bertuzzi, Annalisa Arcari, Luca Zazzeroni, Patrizia Bernuzzi, Noemi Laprovitera, Gianluca Storci, Salvatore Nicola Bertuccio, Manuela Ferracin, Massimiliano Bonafè, Pier Luigi Zinzani, and Francesca Bonifazi
- Subjects
lymphoma ,senescence ,exhaustion ,chimeric antigen receptor (CAR T) ,pembrolizumab ,resistance ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundT cells engineered to target CD19 antigen on neoplastic B cells represent the most striking example of CAR-T cell therapy. The success rate of this therapy is affected by several limitations: target antigen loss, and/or acquisition of a senescent/exhausted phenotype by CAR and non-CAR T cells.Case presentationWe report on a patient affected by refractory Diffuse Large B-cell Lymphoma who was resistant to CAR T-cell therapy and to two cycles post CAR-T of pembrolizumab (PBZ) due to the evolution into a B-cell Hodgkin-like lymphoma. Owing to the CD30 expression and the Hodgkin-like phenotype, the patient was ultimately treated with Brentuximab-Vedotin and finally underwent remission. Upon PBZ treatment, 100% of circulating CAR-T+ cells showed a persistent CD8+ senescent/exhausted phenotype, while an increase in the percentage of senescent cells was found in the non-CAR CD8+ T cells compartment.ConclusionsPBZ is not able to reinvigorate exhausted CAR+ T cells and to confer durable clinical response. We hypothesize that the phenomenon is due to the senescent phenotype of CAR+ T cells, which did not allow PBZ-induced reactivation and proliferative rescue. The phenomenon, together with the loss of CAR-T target CD19 and the shift of non-CAR CD8+ T cells towards a senescent phenotype likely contributed to set up an immune landscape with poor antitumor capacity.
- Published
- 2022
- Full Text
- View/download PDF
7. Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK)
- Author
-
Michele Fiore, Alberto Taddia, Valentina Indio, Salvatore Nicola Bertuccio, Daria Messelodi, Salvatore Serravalle, Jessica Bandini, Filippo Spreafico, Daniela Perotti, Paola Collini, Andrea Di Cataldo, Gianandrea Pasquinelli, Francesca Chiarini, Maura Fois, Fraia Melchionda, Andrea Pession, and Annalisa Astolfi
- Subjects
CCSK ,FGF3 ,BCOR ,internal tandem duplication ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms’ tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases (p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.
- Published
- 2023
- Full Text
- View/download PDF
8. Are Induced Pluripotent Stem Cells a Step towards Modeling Pediatric Leukemias?
- Author
-
Salvatore Nicola Bertuccio, Davide Leardini, Daria Messelodi, Laura Anselmi, Francesca Manente, Federico Ragni, Salvatore Serravalle, Riccardo Masetti, and Andrea Pession
- Subjects
pediatric leukemia ,in vitro modeling ,iPSCs ,genome editing ,new target therapies ,Cytology ,QH573-671 - Abstract
Despite enormous improvements in pre-clinical and clinical research, acute leukemia still represents an open challenge for pediatric hematologists; both for a significant relapse rate and for long term therapy-related sequelae. In this context, the use of an innovative technology, such as induced pluripotent stem cells (iPSCs), allows to finely reproduce the primary features of the malignancy and can be exploited as a model to study the onset and development of leukemia in vitro. The aim of this review is to explore the recent literature describing iPSCs as a key tool to study different types of hematological malignancies, comprising acute myeloid leukemia, non-down syndrome acute megakaryoblastic leukemia, B cell acute lymphoblastic leukemia, and juvenile myelomonocytic leukemia. This model demonstrates a positive impact on pediatric hematological diseases, especially in those affecting infants whose onsets is found in fetal hematopoiesis. This evidence highlights the importance of achieving an in vitro representation of the human embryonic hematopoietic development and timing-specific modifications, either genetic or epigenetic. Moreover, further insights into clonal evolution studies shed light in the way of a new precision medicine era, where patient-oriented decisions and therapies could further improve the outcome of pediatric cases. Nonetheless, we will also discuss here the difficulties and limitations of this model.
- Published
- 2022
- Full Text
- View/download PDF
9. iPSC-Derived Gaucher Macrophages Display Growth Impairment and Activation of Inflammation-Related Cell Death
- Author
-
Daria Messelodi, Salvatore Nicola Bertuccio, Valentina Indio, Silvia Strocchi, Alberto Taddia, Salvatore Serravalle, Jessica Bandini, Annalisa Astolfi, and Andrea Pession
- Subjects
Gaucher disease ,iPSC ,macrophages ,inflammation ,necroptosis ,Cytology ,QH573-671 - Abstract
Gaucher disease is a lysosomal storage disorder characterized by β-glucosidase enzyme deficiency and substrate accumulation, especially in cells of the reticuloendothelial system. Typical features of the disease are the unrestrained activation of inflammatory mechanisms, whose molecular pathways are still unclear. To investigate biological mechanisms underlying the macrophage activation in GD, we derived iPSCs from a healthy donor and a GD patient line and differentiated them into hematopoietic progenitors. While GD iPSCs are able to efficiently give rise to CD33+/CD45+ myeloid progenitors, the maturation towards the CD14+/CD163+ monocyte/macrophages fate resulted enhanced in the GD lines, that in addition displayed a decreased growth potential compared to control cells either in semisolid or in liquid culture. The GD lines growth impairment was associated with a significant upregulation of RIPK3 and MLKL, two key effectors of necroptosis, the inflammation related cell death pathway. The activation of necroptosis, which has already been linked to neuronopathic GD, may play a role in the disease proinflammatory condition and in the identified cell growth defects. Understanding the GD macrophage role in the alteration of mechanisms linked to cellular metabolism imbalance, cell death and inflammation are crucial in identifying new ways to approach the disease.
- Published
- 2021
- Full Text
- View/download PDF
10. ERCC6L2-related disease: a novel entity of bone marrow failure disorder with high risk of clonal evolution
- Author
-
Francesco Baccelli, Davide Leardini, Sara Cerasi, Daria Messelodi, Salvatore Nicola Bertuccio, and Riccardo Masetti
- Subjects
Hematology ,General Medicine - Abstract
ERCC excision repair 6 like 2 (ERCC6L2) gene encodes for different helicase-like protein members of the Snf2 family involved in transcription-coupled nucleotide excision repair and in cell proliferation. Germline homozygous mutations in children and adults predispose to a peculiar bone marrow failure phenotype characterized by mild hematological alterations with a high risk of developing acute myeloid leukemia. The outcome for patients with leukemia progression is dismal while patients undergoing hematopoietic stem cell transplantation in the early stage have better outcomes. The ERCC6L2-related hematological disease presents a high penetrance, posing important questions regarding the treatment strategies and possible preemptive approaches. This review describes the biological function of ERCC6L2 and the clinical manifestations of the associated disease, trying to focus on the unsolved clinical questions.
- Published
- 2023
11. Torque teno mini virus as a cause of childhood acute promyelocytic leukemia lacking PML/RARA fusion
- Author
-
Matteo Carella, Stefano Volinia, Riccardo Masetti, Salvatore Nicola Bertuccio, Virginia Libri, Andrea Pession, Valentina Indio, Simone Rampelli, Annalisa Astolfi, Davide Leardini, Marco Candela, Daria Messelodi, Jessica Bandini, Salvatore Serravalle, Astolfi A., Masetti R., Indio V., Bertuccio S.N., Messelodi D., Rampelli S., Leardini D., Carella M., Serravalle S., Libri V., Bandini J., Volinia S., Candela M., and Pession A.
- Subjects
Torque teno mini virus ,Oncogene Proteins, Fusion ,business.industry ,Karyotype ,Immunology ,Tretinoin ,Cell Biology ,Hematology ,Biochemistry ,Virology ,Antineoplastic Agent ,Leukemia, Promyelocytic, Acute ,Medicine ,Female ,Child ,business ,Human ,Childhood Acute Promyelocytic Leukemia - Abstract
Astolf et al provide the first report of acute promyelocytic leukemia driven by viral insertion into the RARA locus. This represents a clear demonstration of a pathology driven by the member of the anelloviruses, a group of viruses otherwise thought to have minimal or no pathogenic potential.
- Published
- 2021
12. Mesenchymal Stromal Cell Secretome in Acute Myeloid Leukemia Bone Marrow Niche
- Author
-
Giulia Borella, Giorgia Longo, Ambra Da Ros, Elisabetta Campodoni, Margherita Montanari, Maddalena Benetton, Salvatore Nicola Bertuccio, Monica Sandri, Claudia Tregnago, Riccardo Masetti, Franco Locatelli, and Martina Pigazzi
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
13. iPSC-Derived Gaucher Macrophages Display Growth Impairment and Activation of Inflammation-Related Cell Death
- Author
-
Annalisa Astolfi, Andrea Pession, Jessica Bandini, Salvatore Nicola Bertuccio, Alberto Taddia, Salvatore Serravalle, Valentina Indio, Silvia Strocchi, Daria Messelodi, Messelodi D., Bertuccio S.N., Indio V., Strocchi S., Taddia A., Serravalle S., Bandini J., Astolfi A., and Pession A.
- Subjects
Necroptosi ,Programmed cell death ,Macrophage ,QH301-705.5 ,Protein Kinase ,Necroptosis ,Induced Pluripotent Stem Cells ,necroptosis ,Monocyte ,Induced Pluripotent Stem Cell ,Article ,Monocytes ,Proinflammatory cytokine ,medicine ,Humans ,Cell Lineage ,Biology (General) ,Progenitor cell ,Cell Proliferation ,Inflammation ,iPSC ,Gaucher Disease ,Cell Death ,Chemistry ,Cell growth ,Macrophages ,Cell Differentiation ,General Medicine ,Macrophage Activation ,Cell biology ,medicine.anatomical_structure ,Receptor-Interacting Protein Serine-Threonine Kinases ,CD163 ,Protein Kinases ,Human - Abstract
Gaucher disease is a lysosomal storage disorder characterized by β-glucosidase enzyme deficiency and substrate accumulation, especially in cells of the reticuloendothelial system. Typical features of the disease are the unrestrained activation of inflammatory mechanisms, whose molecular pathways are still unclear. To investigate biological mechanisms underlying the macrophage activation in GD, we derived iPSCs from a healthy donor and a GD patient line and differentiated them into hematopoietic progenitors. While GD iPSCs are able to efficiently give rise to CD33+/CD45+ myeloid progenitors, the maturation towards the CD14+/CD163+ monocyte/macrophages fate resulted enhanced in the GD lines, that in addition displayed a decreased growth potential compared to control cells either in semisolid or in liquid culture. The GD lines growth impairment was associated with a significant upregulation of RIPK3 and MLKL, two key effectors of necroptosis, the inflammation related cell death pathway. The activation of necroptosis, which has already been linked to neuronopathic GD, may play a role in the disease proinflammatory condition and in the identified cell growth defects. Understanding the GD macrophage role in the alteration of mechanisms linked to cellular metabolism imbalance, cell death and inflammation are crucial in identifying new ways to approach the disease.
- Published
- 2021
14. AML-283 The Genetic Landscape of NUP98-Rearranged Pediatric Leukemia
- Author
-
Masayuki Umeda, Nicole Michmerhuizen, Jing Ma, Tamara Westover, Michael P Walsh, Guangchun Song, Cristina Mecucci, Danika Di Giacomo, Franco Locatelli, Riccardo Masetti, Salvatore Nicola Bertuccio, Martina Pigazzi, Ilaria Iacobucci, Charles G Mullighan, and Jeffery M Klco
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2022
15. Poster: AML-283 The Genetic Landscape of NUP98-Rearranged Pediatric Leukemia
- Author
-
Masayuki Umeda, Nicole Michmerhuizen, Jing Ma, Tamara Westover, Michael P Walsh, Guangchun Song, Cristina Mecucci, Danika Di Giacomo, Franco Locatelli, Riccardo Masetti, Salvatore Nicola Bertuccio, Martina Pigazzi, Ilaria Iacobucci, Charles G Mullighan, and Jeffery M Klco
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2022
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.