320 results on '"A. Martini"'
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2. Prognostic Value of Body Composition in a Cohort of Elderly Pts with Newly Diagnosed Classical Hodgkin's Lymphoma: A Retrospective Single Center Study
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Serageldin Kamel, Joo Schmidt, Eslam Aboismail, Lucia L Martini, Sairah Ahmed, Ranjit Nair, Raphael E Steiner, Michael L. Wang, Gregory Ravizzini, Sarita Soebianto, Tinsu Pan, Jillian R. Gunther, Chelsea C. Pinnix, and Hun Ju Lee
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
3. Study of Venetoclax Plasma Concentrations during Co-Administration with Posaconazole in Acute Myeloid Leukemia (AML) Patients
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Zappasodi, Patrizia, primary, De Gregori, Simona, additional, Gelli, Eleonora, additional, Roncoroni, Elisa, additional, Rossi, Marianna, additional, Tobar Cabrera, Claudia Patricia, additional, Santacroce, Eugenio, additional, Martini, Gianluca, additional, Calabretta, Ludovica, additional, Albertini, Riccardo, additional, and Arcaini, Luca, additional
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- 2022
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4. Association between Myocardial Iron Overload and Diffuse Myocardial Fibrosis in Thalassemia Major
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Meloni, Antonella, primary, Pistoia, Laura, additional, Positano, Vincenzo, additional, De Luca, Antonio, additional, Martini, Nicola, additional, Murgia, Mauro, additional, Barone, Angelica, additional, Sanna, Maria Grazia, additional, Gentili, Sara, additional, Massa, Antonella, additional, Maggio, Aurelio, additional, Sinagra, Gianfranco, additional, Pepe, Alessia, additional, and Cademartiri, Filippo, additional
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- 2022
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5. Prognostic Value of Body Composition in a Cohort of Elderly Pts with Newly Diagnosed Classical Hodgkin's Lymphoma: A Retrospective Single Center Study
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Kamel, Serageldin, primary, Schmidt, Joo, additional, Aboismail, Eslam, additional, Martini, Lucia L, additional, Ahmed, Sairah, additional, Nair, Ranjit, additional, Steiner, Raphael E, additional, Wang, Michael L., additional, Ravizzini, Gregory, additional, Soebianto, Sarita, additional, Pan, Tinsu, additional, Gunther, Jillian R., additional, Pinnix, Chelsea C., additional, and Lee, Hun Ju, additional
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- 2022
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6. Lyn-mediated procaspase 8 dimerization blocks apoptotic signaling in B-cell chronic lymphocytic leukemia
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Zonta, Francesca, Pagano, Mario Angelo, Trentin, Livio, Tibaldi, Elena, Frezzato, Federica, Gattazzo, Cristina, Martini, Veronica, Trimarco, Valentina, Mazzorana, Marco, Bordin, Luciana, Semenzato, Gianpietro, and Brunati, Anna Maria
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- 2014
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7. Study of Venetoclax Plasma Concentrations during Co-Administration with Posaconazole in Acute Myeloid Leukemia (AML) Patients
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Patrizia Zappasodi, Simona De Gregori, Eleonora Gelli, Elisa Roncoroni, Marianna Rossi, Claudia Patricia Tobar Cabrera, Eugenio Santacroce, Gianluca Martini, Ludovica Calabretta, Riccardo Albertini, and Luca Arcaini
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
8. Association between Myocardial Iron Overload and Diffuse Myocardial Fibrosis in Thalassemia Major
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Antonella Meloni, Laura Pistoia, Vincenzo Positano, Antonio De Luca, Nicola Martini, Mauro Murgia, Angelica Barone, Maria Grazia Sanna, Sara Gentili, Antonella Massa, Aurelio Maggio, Gianfranco Sinagra, Alessia Pepe, and Filippo Cademartiri
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
9. Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia
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Teramo, Antonella, Gattazzo, Cristina, Passeri, Francesca, Lico, Albana, Tasca, Giulia, Cabrelle, Anna, Martini, Veronica, Frezzato, Federica, Trimarco, Valentina, Ave, Elisa, Boscaro, Elisa, Piazza, Francesco, Facco, Monica, Trentin, Livio, Semenzato, Gianpietro, and Zambello, Renato
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- 2013
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10. Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome
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Giona, Fiorina, Teofili, Luciana, Moleti, Maria Luisa, Martini, Maurizio, Palumbo, Giovanna, Amendola, Angela, Mazzucconi, Maria Gabriella, Testi, Anna Maria, Pignoloni, Patrizia, Orlando, Sonia Maria, Capodimonti, Sara, Nanni, Mauro, Leone, Giuseppe, Larocca, Luigi Maria, and Foà, Robin
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- 2012
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11. Endothelial progenitor cells are clonal and exhibit the JAK2V617F mutation in a subset of thrombotic patients with Ph-negative myeloproliferative neoplasms
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Teofili, Luciana, Martini, Maurizio, Iachininoto, Maria Grazia, Capodimonti, Sara, Nuzzolo, Eugenia Rosa, Torti, Lorenza, Cenci, Tonia, Larocca, Luigi Maria, and Leone, Giuseppe
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- 2011
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12. ISB 1442, a First-in-Class CD38 and CD47 Bispecific Antibody Innate Cell Modulator for the Treatment of Relapsed Refractory Multiple Myeloma
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Stefano, Sammicheli, primary, Grandclement, Camille, additional, Dehilly, Elie, additional, Panagopoulou, Maria, additional, Martini, Evangelia, additional, Castillo, Rosa, additional, Suere, Perrine, additional, Pouleau, Blandine, additional, Estoppey, Carole, additional, Frei, Julia, additional, Loyau, Jeremy, additional, Monney, Thierry, additional, Wood, Rebecca, additional, Croset, Amelie, additional, Rubod, Alain, additional, Gudi, Girish, additional, Udupa, Venkatesha, additional, Gn, Sunitha, additional, Menon, Vinu, additional, Rasmussen, Daniel, additional, Olsen, Jeppe Koch, additional, Giovannini, Roberto, additional, Chakrapani, Aravind, additional, Blein, Stanislas, additional, Doucey, Marie-Agnes, additional, Drake, Adam, additional, Riva, Alessandro, additional, Konto, Cyril, additional, Perro, Mario, additional, and Mbow, Lamine, additional
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- 2021
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13. Expansion, Persistence, and Characteristics of Autologous, Bhv-1100 Armored Memory-like NK Cells Infused Prior to Autologous Stem Cell Transplant in MRD+ Multiple Myeloma Patients: A First-in-Human Trial
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Birch, Grace Caroline, Vergara-Cadavid, Juliana, Maqbool, Mohsin, Martini, Alba, Dinh, Khanlinh, Shapiro, Roman M., Ansuinelli, Michela, Nguyen, Tuyet, Reynolds, Carol, Soo Y, Im, Wei, Hope, Hogan, Sarah, Kendricken, Elizabeth, Sperling, Adam S., Nadeem, Omar, Laubach, Jacob, Rybicki, Alissa, Schnittman, Steven, Stock, Elyse, Hernandez Rodriguez, Diego, Daley, Heather, Nikiforow, Sarah, Ritz, Jerome, Soiffer, Robert J., Bianchi, Giada, and Romee, Rizwan
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- 2023
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14. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity
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Pende, Daniela, Marcenaro, Stefania, Falco, Michela, Martini, Stefania, Bernardo, Maria Ester, Montagna, Daniela, Romeo, Elisa, Cognet, Céline, Martinetti, Miryam, Maccario, Rita, Mingari, Maria Cristina, Vivier, Eric, Moretta, Lorenzo, Locatelli, Franco, and Moretta, Alessandro
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- 2009
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15. Myocardial Tissue Characterization By T2 Mapping in Thalassemia Major
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Pepe, Alessia, primary, Martini, Nicola, additional, Borrello, Rita, additional, Positano, Vincenzo, additional, Pistoia, Laura, additional, Maggio, Aurelio, additional, Guerrini, Giulia, additional, Sorrentino, Francesco, additional, Paci, Cristina, additional, Visceglie, Domenico, additional, Pedrinelli, Roberto, additional, and Meloni, Antonella, additional
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- 2020
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16. Treatment Patterns and Clinical Outcomes of Patients with Sézary Syndrome at Emory University
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Martini, Dylan J, primary, Goyal, Subir, additional, Switchenko, Jeffrey M., additional, Lechowicz, Mary Jo, additional, and Allen, Pamela B., additional
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- 2020
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17. Native T1 Values and Cardiac Involvement in Patients with Thalassemia Major
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Pepe, Alessia, primary, Martini, Nicola, additional, De Luca, Antonio, additional, Positano, Vincenzo, additional, Pistoia, Laura, additional, Borsellino, Zelia, additional, Carrai, Valentina, additional, Sanna, Maria Grazia, additional, Bitti, Pier Paolo, additional, Gentili, Sara, additional, Maggio, Aurelio, additional, Sinagra, Gianfranco, additional, and Meloni, Antonella, additional
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- 2020
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18. Association between Native Myocardial T1 Mapping and Cardiac Function and Macroscopic Fibrosis in Thalassemia Major
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Pepe, Alessia, primary, Martini, Nicola, additional, De Luca, Antonio, additional, Positano, Vincenzo, additional, Pistoia, Laura, additional, Ruffo, Giovan Battista, additional, Serra, Marilena, additional, Gerardi, Calogera, additional, Benni, Monica, additional, Argento, Crocetta, additional, Maggio, Aurelio, additional, Sinagra, Gianfranco, additional, and Meloni, Antonella, additional
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- 2020
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19. Myocardial Tissue Characterization By T2 Mapping in Thalassemia Major
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Antonella Meloni, Alessia Pepe, Francesco Sorrentino, Roberto Pedrinelli, Nicola Martini, Domenico Visceglie, Vincenzo Positano, Rita Borrello, Giulia Guerrini, Laura Pistoia, Cristina Paci, and Aurelio Maggio
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medicine.medical_specialty ,Myocardial tissue ,medicine.diagnostic_test ,business.industry ,Thalassemia ,Healthy population ,T2 mapping ,Immunology ,Magnetic resonance imaging ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Edema ,Internal medicine ,medicine ,Cardiology ,In patient ,medicine.symptom ,business ,Subclinical infection - Abstract
Introduction.The presence of iron deposits results in a significant reduction in all magnetic resonance imaging (MRI) relaxation times (T1, T2 and T2*). In the clinical setting the T2* technique is the method of choice for cardiac iron quantification and it has revolutionized the management of patients with hemoglopinopathies. Purpose.To compare myocardial T2 against T2* in patients with thalassemia major (TM) for myocardial iron characterization. Methods.133 TM patients (79 females, 38.4±11.3 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered. T2 and T2* images were acquired, respectively, with multi-echo fast-spin-echo and gradient-echo sequences. Global heart T2 and T2* values were obtained by averaging the values in all 16 myocardial segments. The normal T2 range was established as mean±2 standard deviations on data acquired on 80 healthy volunteers (males: 48-56 ms and females: 50-57 ms). The lower limit of normal for global heart T2*, established on the same healthy population, was 32 ms. Results.A significant correlation was detected between global heart T2 and T2* values (R=0.577; P Out of the 113 (84.9%) patients with a normal global heart T2* value, none had a decreased global heart T2 value, while 58 (51.3%) had an increased T2 value. Out of the 20 patents with a decreased global heart T2* value, only 10 (50%) had also a reduced T2 value. Conversely, 9 (45.0%) had a normal global heart T2 value and one (4.5) showed an increased T2 value. The 59 patients with increased global heart T2 value were significantly older than the remaining patients (40.8±10.5 vs 36.4±11.6 years; P=0.019) Conclusion.All patients with decreased T2 value had also a decreased T2* value and in half of the patients iron load was undetected by T2, suggesting that T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment. However, more than half of TM patients had an increased T2 value, thus may be caused by the presence of myocardial inflammation and/or edema. So, T2 mapping could reveal subclinical myocardial involvement in TM patients. Figure Disclosures Pistoia: Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.
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- 2020
20. Treatment Patterns and Clinical Outcomes of Patients with Sézary Syndrome at Emory University
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Dylan J. Martini, Pamela B. Allen, Mary Jo Lechowicz, Jeffrey M. Switchenko, and Subir Goyal
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medicine.medical_specialty ,Univariate analysis ,Chemotherapy ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Systemic therapy ,Lymphoma ,Exact test ,Internal medicine ,Cohort ,medicine ,business ,Prospective cohort study - Abstract
Introduction Sézary syndrome (SS) is an aggressive, leukemic subtype of cutaneous T-cell lymphoma (CTCL) with a median survival of 3-5 years. Approved therapies include skin-directed therapy, radiation, and systemic therapies such as chemotherapy, histone deacetylase (HDAC) inhibitors, interferon, extracorporeal photopheresis (ECP), and oral retinoids. There is no consensus first-line therapy for SS and there is limited data regarding prognostic biomarkers. We assessed treatment patterns, outcomes, and racial differences at our institution. Methods We performed a retrospective review of 62 patients at Winship Cancer Institute of Emory University from 1990-2020 with a confirmed diagnosis of SS. Clinical data collected from the electronic medical record included demographics, baseline laboratory values, disease characteristics, and therapy. Clinical outcomes were measured by overall survival (OS) and time to next treatment (TTNT). OS was measured from time of diagnosis to date of death or last follow-up. TTNT was defined as the number of months from the start of the first line of therapy until the initiation of the subsequent therapeutic regimen. Descriptive analysis was performed for each variable and a comparison between African American (AA) and white patients was performed using ANOVA for numerical covariates and chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS and TTNT were generated for the whole cohort. A Kaplan-Meier curve was also generated to compare time from diagnosis to initiation of first systemic therapy stratified by race along with the log-rank p-value. The univariate association of baseline variables with OS and TTNT was assessed by Cox proportional hazards models and the multivariable analyses (MVA) were performed on variables that had p-value less than 0.05 on univariate analyses. Results Males made up (58.1%) of our patients and the median age at diagnosis was 65.9 years. Nearly one-half (45.2%) of patients were AA. The median Sézary count at diagnosis was 1320 cells/uL. The median time from diagnosis to first systemic therapy was 2.4 months and the median number of systemic therapies was 3.0. Information regarding systemic treatments received after diagnosis is presented inTable 1. The most common first-line systemic therapies were oral retinoids (43.5%), ECP (32.3%), and interferon (30.6%). HDAC inhibitors and total skin electron beam (TSEB) radiation were common treatments beyond first line (46.8% received HDAC inhibitors, 38.7% received TSEB), but were rarely used in the first-line setting. The median OS and TTNT were 3.1 years and 6.3 months, respectively(Figure 1). In MVA, elevated WBC and LDH were significantly associated with shorter OS (WBC HR: 1.05, 95% CI: 1.01-1.08, p=0.01; LDH HR: 1.003, 95% CI: 1.001-1.005, p=0.011) and shorter TTNT (WBC HR: 1.04, 95% CI: 1.002-1.08, p=0.041; LDH HR: 1.002, 95% CI: 1.001-1.004, p=0.048). In analysis by race, AA patients had a higher proportion of females compared to non-hispanic white patients (53.6% vs 28.1%, p=0.045). AA patients also had lower median hemoglobin at diagnosis (12.6 vs 14.3, p=0.036), higher median LDH at diagnosis (360 vs 232, p=0.002), and longer median time from diagnosis to first systemic therapy compared to non-hispanic white patients (3.17 months vs 2.14 months, p=0.039,Figure 2). Conclusions SS is an aggressive subtype of CTCL with no consensus first-line therapy and limited data on prognostic biomarkers. In our cohort, oral retinoids, ECP, and interferon were the most commonly utilized treatments in the first-line setting. Elevated WBC and LDH were significantly associated with both OS and TTNT which suggests that these may have value as prognostic biomarkers in SS. AA patients may have delayed time from diagnosis to starting systemic therapy and higher LDH at diagnosis. This data is hypothesis-generating and should be validated in larger, prospective studies. Disclosures Allen: Bayer:Consultancy, Other;Imbrium:Consultancy, Other;Research to Practice:Speakers Bureau;Clinical Care Options:Speakers Bureau;Curio Sciences:Honoraria.
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- 2020
21. Native T1 Values and Cardiac Involvement in Patients with Thalassemia Major
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Zelia Borsellino, Valentina Carrai, Gianfranco Sinagra, Aurelio Maggio, Sara Gentili, Maria Grazia Sanna, Nicola Martini, Vincenzo Positano, Alessia Pepe, Laura Pistoia, Pier Paolo Bitti, Antonio De Luca, and Antonella Meloni
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Thalassemia ,Immunology ,Myocardial iron ,Magnetic resonance imaging ,Cell Biology ,Hematology ,Gold standard (test) ,medicine.disease ,Biochemistry ,medicine.anatomical_structure ,Ventricle ,Internal medicine ,Heart failure ,medicine ,Cardiology ,In patient ,Chelation therapy ,business - Abstract
Background.The T2* cardiovascular magnetic resonance (CMR) is the gold standard for the non invasive detection of myocardial iron overload (MIO). The native myocardial T1 mapping has been proposed as a complementary tool, thanks to its higher sensitivity in presence of small amounts of iron, but no data are available in literature about its clinical impact. Objective:To explore the clinical impact of T1 mapping for detecting cardiac complications in thalassemia major (TM). Methods.We considered 146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Three parallel short-axis slices of the left ventricle (LV) were acquired with the Modified Look-Locker Inversion recovery (MOLLI) sequence. The native T1 values in all 16 myocardial segments were obtained and the global value was the mean. Results.Twenty-one patients had an history of cardiac complications: 11 heart failure, 8 arrhythmias (7 supraventricular and 1 ventricular), and 2 pulmonary hyperthension. Patients with cardiac complications had significantly lower global heart T1 values (879.3±121.9 ms vs 963.2±98.5 ms; P Conclusion:We found out a significant association between decreased native global heart T1 values and a history of cardiac complications, suggesting that an early detection of myocardial iron burden by native T1 can support the clinicians in modifing chelation therapy earlier. Figure Disclosures Pepe: ApoPharma Inc.:Other: no profit support;Bayer:Other: no profit support;Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.
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- 2020
22. Association between Native Myocardial T1 Mapping and Cardiac Function and Macroscopic Fibrosis in Thalassemia Major
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Laura Pistoia, Antonio De Luca, Monica Benni, Marilena Serra, Calogera Gerardi, Antonella Meloni, Aurelio Maggio, Gianfranco Sinagra, Vincenzo Positano, Giovan Battista Ruffo, Nicola Martini, Crocetta Argento, and Alessia Pepe
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Cardiac function curve ,medicine.medical_specialty ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Thalassemia ,Immunology ,Myocardial iron ,Magnetic resonance imaging ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Hypokinesia ,Fibrosis ,Internal medicine ,medicine ,Cardiology ,Myocardial fibrosis ,medicine.symptom ,business - Abstract
Background.Cardiovascular magnetic resonance (CMR) is the only available technique for the non-invasive quantification of MIO. The native T1 mapping has recently been proposed as an alternative to the universally adopted T2* technique, due to the higher sensitivity for detection of changes associated with mild or early iron overload. Objective.To study the association between T1 values and left ventricular (LV) function in thalassemia major (TM) and to evaluate for the first time if T1 measurements quantifying MIO are influenced by macroscopic myocardial fibrosis. Methods.146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent CMR. Native T1 values were obtained by Modified Look-Locker Inversion recovery (MOLLI) sequence in all 16 myocardial segments and the global value was the mean. LV function parameters were quantified by cine images. Late gadolinium enhancement (LGE) technique was used to detect macroscopic myocardial fibrosis. Results.No correlation was detected between global heart T1 values and LV volume indexes, LV mass index, or LV ejection fraction. Foourteen (9.6%) patients had an abnormal LV motion (13 hypokinesia and 1 dyskinesia) and they showed significantly lower global heart T1 values than patients without LV motion abnormalities (883.8±139.7 ms vs 959.0±91.3 ms; P=0.049). LGE images were acquired in 88 patients (60.3%) and macroscopic myocardial fibrosis was detected in 36 patients (40.9%). The 72.2% of patients had two or more foci of fibrosis. Patients with macroscopic myocardial fibrosis had significantly lower global heart T1 values (921.3±100.3 ms vs 974.5±72.7 ms; P=0.027) (Figure 1A). Data about the LGE was present for 1408 segments (88 patients x 16 segments) and 105 (7.5%) were positive. Segments with LGE had significantly lower T1 values than segments LGE-negative (905.6±110.6 ms vs 956.9±103.8 ms; P Conclusion.No correlation between T1 values and LV function parameters was detected, probably because the majority of the patients had normal or mild abnormal LV parameters. TM patients with macroscopic myocardial fibrosis showed significantly lower T1 values suggesting that T1 measurements for quantifying MIO are not influenced by macroscopic myocardial fibrosis and an association between myocardial iron and macroscopic fibrosis, previously detected only in pediatric TM patients. Figure Disclosures Pepe: Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria;Bayer:Other: no profit support;ApoPharma Inc.:Other: no profit support.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.
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- 2020
23. Mutational Profile of Leukemic Stem Cells in FLT3-ITD Mutated AML
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Ottone, Tiziana, primary, Travaglini, Serena, additional, Alfonso, Valentina, additional, Angelini, Daniela, additional, Guerrera, Gisella, additional, Lavorgna, Serena, additional, Divona, Mariadomenica, additional, Nardozza, Anna Maria, additional, Cristiano, Antonio, additional, irno Consalvo, Maria, additional, de Bardi, Marco, additional, Neri, Benedetta, additional, Marchesi, Francesco, additional, Gurnari, Carmelo, additional, Paterno, Giovangiacinto, additional, Martini, Vincenza, additional, Battistini, Luca, additional, Venditti, Adriano, additional, Buccisano, Francesco, additional, Arcese, William, additional, Lo-Coco, Francesco, additional, and Voso, Maria Teresa, additional
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- 2019
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24. Acute Promyelocytic Leukemia (APL) in Very Elderly Patients: Real-Life behind Protocols
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Rosati, Serena, primary, Breccia, Massimo, additional, Gurnari, Carmelo, additional, Carmosino, Ida, additional, Scalzulli, Emilia, additional, Montefusco, Enrico, additional, Perrone, Salvatore, additional, Annibali, Ombretta, additional, Martini, Vincenza, additional, Trapè, Giulio, additional, Trawinska, Malgorzata Monika, additional, Minotti, Clara, additional, Cimino, Giuseppe, additional, Tafuri, Agostino, additional, Avvisati, Giuseppe, additional, Voso, Maria Teresa, additional, Foà, Robin, additional, and Latagliata, Roberto, additional
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- 2019
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25. Analysis of the receptor-ligand interactions in the natural killer–mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112)
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Pende, Daniela, Spaggiari, Grazia Maria, Marcenaro, Stefania, Martini, Stefania, Rivera, Paola, Capobianco, Andrea, Falco, Michela, Lanino, Edoardo, Pierri, Ivana, Zambello, Renato, Bacigalupo, Andrea, Mingari, Maria Cristina, Moretta, Alessandro, and Moretta, Lorenzo
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- 2005
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26. Cardiac involvement in Erdheim-Chester disease: an MRI study
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Alessandro Palumbo, Gaia Manari, Augusto Vaglio, Enrica Rossi, Chiara Martini, Lorenzo Buttarelli, Massimo De Filippo, and Davide Gianfreda
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Adult ,Male ,Erdheim-Chester Disease ,Pathology ,medicine.medical_specialty ,genetic structures ,Immunology ,Long bone ,030204 cardiovascular system & hematology ,Biochemistry ,Magnetic resonance angiography ,03 medical and health sciences ,Osteosclerosis ,0302 clinical medicine ,Humans ,Medicine ,Aorta ,Histiocyte ,Aged ,medicine.diagnostic_test ,business.industry ,CD68 ,Magnetic resonance imaging ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Aortic Aneurysm ,Histiocytosis ,medicine.anatomical_structure ,Echocardiography ,030220 oncology & carcinogenesis ,Erdheim–Chester disease ,Female ,business ,Magnetic Resonance Angiography - Abstract
To the editor: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (
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- 2016
27. G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch
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Paglialunga, Francesca, Fico, Annalisa, Iaccarino, Ingram, Notaro, Rosario, Luzzatto, Lucio, Martini, Giuseppe, and Filosa, Stefania
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- 2004
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28. Acute Promyelocytic Leukemia (APL) in Very Elderly Patients: Real-Life behind Protocols
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Ombretta Annibali, Massimo Breccia, Maria Teresa Voso, Carmelo Gurnari, Giulio Trapè, Giuseppe Cimino, Malgorzata Monika Trawinska, Serena Rosati, Enrico Montefusco, Agostino Tafuri, Ida Carmosino, Salvatore Perrone, Emilia Scalzulli, Vincenza Martini, Robin Foà, Clara Minotti, Giuseppe Avvisati, and Roberto Latagliata
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medicine.medical_specialty ,business.industry ,education ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Clinical trial ,Consolidation therapy ,Regimen ,Family medicine ,Cohort ,Honorarium ,Medicine ,Frail elderly ,Lost to follow-up ,business ,health care economics and organizations - Abstract
Introduction APL in the elderly is rare and about 5% of patients with APL are older than 70 years at diagnosis; compared to young adults, prognosis of older patients with APL remains poorer, due to the presence of severe comorbidities and the higher rate of mortality related to induction or consolidation therapy. Aim To evaluate in an unselected real-life cohort of APL patients aged ≥ 70 years the true efficacy of targeted treatments and follow-up of disease. Methods A retrospective cohort of 45 consecutive APL patients (M/F 27/18), aged ≥ 70 years and diagnosed at 8 different hematologic institutions in Lazio, Italy, from July 1991 to May 2019 was analyzed. To avoid possible selection bias, particular attention was given to consider also patients managed outside of clinical trials because of comorbidities at diagnosis and patients dead immediately after APL diagnosis before starting any treatment. Results The median age at diagnosis was 76.6 years (range 70 - 87.1). The main clinical features at diagnosis are shown in Table 1. As to major comorbidities, 28 patients(62.2%) had concomitant cardiologic diseases, 13 (28.8%) had a clinical history of cancer and 11 (24.4%) were affected by diabetes. Forty-three patients (95.5%) started therapy after diagnosis, 2 (4.4%) died before starting treatment from early hemorrhagic complications. Twenty-two patients (51.1%) (Group A) were enrolled in clinical controlled trials or were treated according to clinical controlled trials [13 pts (59.0%) according to AIDA-like regimen, 9 (40.9%) according to APL0406 study], while 21 patients (48,8%) (Group B) received an ATRA-based personalized approach. Overall, complete morphologic remission (CR) after induction therapy was achieved in 33 patients (76.7%); all patients in the Group A achieved CR compared to 11 patients (52.3%) in the Group B (p Conclusions: The present analysis of an unselected cohort of APL patients aged ≥ 70 years highlights that almost half of the patients were not considered eligible for a standard approach as in youngers, and received sub-optimal induction treatments, with a very high rate of early death and dismal rates of CR and OS compared to patients treated with standard therapy. As a consequence, it is mandatory, whenever possible, to adopt standard therapies instead of modified/reduced personalized approaches also in frail elderly patients with APL, to improve their outcome. Disclosures Breccia: BMS: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Celgene: Honoraria. Trawinska:Novartis: Consultancy, Honoraria. Foà:Celltrion: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Latagliata:Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Pfizer: Honoraria.
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- 2019
29. Mutational Profile of Leukemic Stem Cells in FLT3-ITD Mutated AML
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Serena Travaglini, Giovangiacinto Paterno, Francesco Buccisano, Carmelo Gurnari, Benedetta Neri, Mariadomenica Divona, Antonio Cristiano, Maria Irno Consalvo, Daniela F. Angelini, Maria Teresa Voso, Francesco Lo-Coco, Valentina Alfonso, William Arcese, Serena Lavorgna, Adriano Venditti, Vincenza Martini, Marco De Bardi, Luca Battistini, Gisella Guerrera, Tiziana Ottone, Francesco Marchesi, and Anna Maria Nardozza
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education.field_of_study ,NPM1 ,Myeloid ,Immunology ,Population ,Myeloid leukemia ,Cell Biology ,Hematology ,Biology ,CD38 ,medicine.disease ,Biochemistry ,Somatic evolution in cancer ,Leukemia ,Immunophenotyping ,medicine.anatomical_structure ,medicine ,Cancer research ,education - Abstract
Introduction Persistence of leukemia stem cells (LSCs) in patients with Acute Myeloid Leukemia (AML) achieving complete remission (CR) after chemotherapy leads to disease recurrence and poor outcome. Therefore, the identification of LSCs driving resistance to therapy represents an important challenge. LSCs reside within the CD34+/CD38- cells and it has been recently demonstrated that co-expression of CD99 allows for separation of LSCs from functionally normal hematopoietic stem cells in AML. We showed that the presence of a CD123/CD99/CD25+ population within CD34+ cells strongly correlates with FLT3-ITD-positivity. The aim of this study was to deeply characterize the molecular profile of CD34+/CD123+/CD99+/CD25+ LSCs to shed light on the subclonal architecture of FLT3-ITD+ AML and to track the expansion of mutated clones. Methods Molecular status of FLT3-ITD and NPM1 were investigated at the DNA level in a cohort of 150 de novo AML patients at diagnosis and at relapse, using standard procedures. Clonal evolution of FLT3-ITD mutations was studied at diagnosis in 14 FLT3-ITD mutated AML on sorted bone marrow populations, purified by the Cytoflex High-Speed Cell Sorter using a sequential gating strategy, to separate CD34/CD123/CD99/CD25+ LSCs-, CD34+ precursors (CD123/CD99/CD25-) and T-lymphocytes. Moreover, to characterize the genetic profile of FLT3-ITD-mutated clones, DNA targeted sequencing was performed on 22 cell populations isolated from 7 AML patients, using the Oncomine™ Myeloid Research Assay panel on the Ion Torrent™ S5 sequencer. Results 39 of 150 AML cases were FLT3-ITD+, at a median allelic ratio (AR) of 0.36 (range 0.05-7.9). The FLT3-ITD AR was significantly higher within the rare LSCs compartment as compared to MNC (median AR: 0.78, range 0.42-19.3, vs 0.09, range 0.05-0.6m p1, while the number of LSCs do not seem to expand (Fig 1B). These data confirm that LSCs may persist at rare frequency during progression, still representing the treatment-resistant FLT3-ITD reservoir, driving disease relapse with expansion of more mature, FLT3-ITD positive populations. Aiming at shedding light on the molecular heterogeneity and subclonal structure of AMLs, using targeted NGS we compared the mutational profiles of MNCs to that of highly purified LSCs and/or to the CD34+/CD123-/CD25-/CD99- counterpart (n=7 patients). In 4 cases the same mutation pattern was present in both MNCs and LSCs. In 3 cases we found additional mutations in NRAS, BCOR and KRAS in MNCs, indicating acquisition of other transforming events during maturation (Fig 2A). Furthermore, the variant allele frequency (VAF) of mutations was similar in MNCs and LSCs (p=0.12), while FLT3-ITD and TKD burden was enriched in LSCs (p=0.03) (Fig 2B). Conversely, the NPM1 mutation burden remained almost stable in the different cell subsets (Fig 2C). In conclusion, our study shows that FLT3 mutations occur in early LSCs characterized by the CD34+/CD123+/CD99+/CD25+ immunophenotype, which represent the leukemic reservoir. These data may be the rational for CD99-targeted treatments in FLT3-ITD mutated AML to achieve durable disease eradication. Disclosures Venditti: Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Buccisano:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees.
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- 2019
30. Detection of Myocardial Iron Overload with Magnetic Resonance By Native T1 and T2* Mapping Using a Segmental Approach
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Pepe, Alessia, primary, Pistoia, Laura, additional, Martini, Nicola, additional, De Marchi, Daniele, additional, Barison, Andrea, additional, Maggio, Aurelio, additional, Giovangrossi, Piera, additional, Bulgarelli, Simona, additional, Pasin, F. Mehtap, additional, Sarli, Roberto, additional, Massa, Antonella, additional, Roccamo, Gaetano, additional, Caini, Mauro, additional, Positano, Vincenzo, additional, and Meloni, Antonella, additional
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- 2018
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31. Targeting Ras-Signalling Pathway to Strike Hsf1 and Induce Apoptosis in Chronic Lymphocytic Leukemia
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Raggi, Flavia, primary, Frezzato, Federica, additional, Martini, Veronica, additional, Severin, Filippo, additional, Trimarco, Valentina, additional, Favero, Emanuele, additional, Visentin, Andrea, additional, Facco, Monica, additional, Semenzato, Gianpietro, additional, and Trentin, Livio, additional
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- 2018
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32. Protective Role Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukemia: FOCUS on Subcutaneous Immunoglobulin Formulations
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Visentin, Andrea, primary, Mauro, Francesca Romana, additional, Rosati, Serena, additional, Imbergamo, Silvia, additional, Scomazzon, Edoardo, additional, Pravato, Stefano, additional, Frezzato, Federica, additional, Martini, Veronica, additional, Severin, Filippo, additional, Raggi, Flavia, additional, Foà, Robin, additional, Semenzato, Gianpietro, additional, and Trentin, Livio, additional
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- 2018
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33. An Innovative Integrated Capacity Building Project for Stem Cell Transplantation in the Southern Lazio Region
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Saltarelli, Francesca, primary, Andriani, Alessandro, additional, Martini, Vincenza, additional, Sala, Roberta, additional, De Padua, Laura, additional, Iaconianni, Vincenzo, additional, and Majolino, Ignazio, additional
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- 2018
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34. Three Different Jak2/Stat3-Related Pathways Favor the Survival of Chronic Lymphocytic Leukemia Neoplastic Clone
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Severin, Filippo, primary, Frezzato, Federica, additional, Martini, Veronica, additional, Raggi, Flavia, additional, Trimarco, Valentina, additional, Visentin, Andrea, additional, Facco, Monica, additional, Semenzato, Gianpietro, additional, and Trentin, Livio, additional
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- 2018
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35. Calcium Mobilization in Unfavorable-Prognosis Chronic Lymphocytic Leukemia Patients Mediates Focal Adhesion Kinase (FAK) Cleavage, Thereby Its Activation
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Frezzato, Federica, primary, Martini, Veronica, additional, Severin, Filippo, additional, Raggi, Flavia, additional, Piccoli, Marco, additional, Visentin, Andrea, additional, Scomazzon, Edoardo, additional, Pravato, Stefano, additional, Imbergamo, Silvia, additional, Piazza, Francesco, additional, Facco, Monica, additional, Semenzato, Gianpietro, additional, and Trentin, Livio, additional
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- 2018
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36. Cardiac involvement in Erdheim-Chester disease: an MRI study
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Gianfreda, Davide, Palumbo, Alessandro A., Rossi, Enrica, Buttarelli, Lorenzo, Manari, Gaia, Martini, Chiara, De Filippo, Massimo, and Vaglio, Augusto
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- 2016
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37. Lyn-mediated procaspase 8 dimerization blocks apoptotic signaling in B-cell chronic lymphocytic leukemia
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Gianpietro Semenzato, Elena Tibaldi, Valentina Trimarco, Luciana Bordin, Cristina Gattazzo, Anna Maria Brunati, Federica Frezzato, Veronica Martini, Marco Mazzorana, Mario A. Pagano, Francesca Zonta, and Livio Trentin
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Proteome ,Chronic lymphocytic leukemia ,Blotting, Western ,Immunology ,Apoptosis ,macromolecular substances ,Biochemistry ,Receptor tyrosine kinase ,chemistry.chemical_compound ,Cytosol ,LYN ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,medicine ,Humans ,Electrophoresis, Gel, Two-Dimensional ,Phosphorylation ,Tyrosine ,Cell Proliferation ,Caspase 8 ,biology ,Computational Biology ,Tyrosine phosphorylation ,Cell Biology ,Hematology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Cell biology ,Dasatinib ,src-Family Kinases ,chemistry ,biology.protein ,Protein Multimerization ,Tyrosine kinase ,medicine.drug - Abstract
Lyn, a member of the group of tyrosine kinases named the Src family kinases (SFKs), is overexpressed, associated with an aberrant multiprotein complex and constitutively active in B-cell chronic lymphocytic leukemia (B-CLL) cells, resulting in a high level of tyrosine phosphorylation and contributing to their resistance to apoptosis. By using biochemical and bioinformatics tools, we identified procaspase-8 (procasp8), the caspase-8 zymogen, as a cytosolic target for Lyn in B-CLL cells, the phosphorylation of which at Tyr380 promotes the formation of an inactive procasp8 homodimer. This complex remains segregated in the cytosol and appears to be crucial in mediating the antiapoptotic function of Lyn in this disease. The significance of the Lyn-procasp8 axis in impairing apoptosis in B-CLL cells was further confirmed by pharmacological and genetic inhibition of procasp8, which drastically reduced the apoptosis induced by the SFK inhibitors PP2 and dasatinib. Our data highlight that Lyn's dysregulated expression, activity, and localization in B-CLLs support resistance to cell demise by inhibiting an early player of apoptotic signaling, and potentially broaden the perspectives of developing new strategies for the treatment of this disease.
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- 2014
38. Three Different Jak2/Stat3-Related Pathways Favor the Survival of Chronic Lymphocytic Leukemia Neoplastic Clone
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Flavia Raggi, Andrea Visentin, Veronica Martini, Livio Trentin, Valentina Trimarco, Gianpietro Semenzato, Filippo Severin, Monica Facco, and Federica Frezzato
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Venetoclax ,Chronic lymphocytic leukemia ,Immunology ,Cell Biology ,Hematology ,CD38 ,medicine.disease ,Biochemistry ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,LYN ,hemic and lymphatic diseases ,Ibrutinib ,medicine ,Cancer research ,Phosphorylation ,Clone (B-cell biology) ,B cell - Abstract
INTRODUCTION Chronic lymphoproliferative disorders are characterized by the expansion of malignant lymphocytes, the most common form being Chronic Lymphocytic Leukemia (CLL). Besides intrinsic abnormalities, the acquisition of the transformed phenotype and the diffusion of disease are related to the favorable cross-talking tumor cell-microenvironment. Furthermore, it has been demonstrated that CLL cells own an amplified mitochondrial respiration leading to an increased Reactive Oxygen Species (ROS) production and intrinsic oxidative stress. Several molecules released by microenvironmental partners signal through JAK-STAT pathway. The deregulation of JAK2/STAT3 axis may lead to aberrant activation of STAT3 and, as a result, to tumor development in hematopoietic cells. We previously analyzed STAT3 and JAK2 expression, phosphorylation and localization in normal and leukemic B cells, demonstrating an abnormal activation of this pathway in the neoplastic clone with respect to normal B lymphocytes. We focused on STAT3 constitutive phosphorylation at serine (Ser) 727 residue since it has been recently observed that the presence of mt-STAT3 Ser727 promotes mitochondrial respiration and, generally, cell viability. We hypothesized the involvement of JAK2/STAT3 axis in 3 different pathways: (i) canonical "IL-6 related pathway"; (ii) JAK2/STAT3 - BCR/Lyn crosstalk; (iii) STAT3 effects on mitochondrial regulation. METHODS STAT3 expression and phosphorylation were evaluated by Western Blotting (WB) and Flow Cytometry (FC). Purified cells (2x106 cells/ml) were cultured, and treated with the JAK2 inhibitor AG490 (10, 50 and 100μM) and the STAT3 inhibitor Stattic (5, 7.5, and 10μM) for 24, 48 and 72h. Experiments with AG490 and Stattic were performed with/without MSCs and with/without Ibrutinib (2.5μM) and Venetoclax (1nM). CLL and normal B cell viability was tested with Annexin V/PI test by FC. P-STAT3 Ser727 expression has been correlated with p44/42, SAPK-JNK, NF-kB p65 and p38 MAPK activation by Reverse Phase Protein Microarrays (RPPA) in 57 therapy-free patients presenting good (mutated IGHV, absence of CD38 or normal karyotype) and poor (unmutated IGHV, CD38 expression or 17p deletion) prognostic factors. RESULTS We found that STAT3 was highly expressed in malignant B cells with respect to normal B lymphocytes. We demonstrated that STAT3 and JAK2 were similarly overexpressed in both good and poor prognosis CLL patients. However, a significant correlation between STAT3 expression levels and their overall survival was observed. Considering STAT3 over-expression and its correlation with the clinical outcome in CLL and, according to our hypothesis, we moved forward with the analysis of the three different JAK2/STAT3 pathways. We demonstrated that AG490 and Stattic were able to induce a dose-dependent apoptosis in CLL cells, also bypassing environmental protection. AG490, targeting JAK2, inhibited the phosphorylation of SHP-1 at Ser591, activating the phosphatase. In turn, SHP-1 activation led to Lyn Tyr396 dephosphorylation/inactivation. Treatment with Stattic did not affect Lyn and SHP-1 phosphorylation since this inhibitor acts downstream to AG490. In fact, simultaneous administration of Ibrutinib led to an increase of apoptosis only in Stattic, but not in AG490 treated cells. This confirms a possible dual role of JAK2 inhibition. Venetoclax/AG490 and Venetoclax/Stattic co-treatment did not show an increased cell death rate, consistent with a downstream effect of Venetoclax to both AG490 and Stattic. RPPA analysis demonstrated a correlation between STAT3, Ser727 constitutively phosphorylated in CLL, and P-p44/42 Thr202/Tyr204, P-SAPK-JNK Thr-183/Tyr185, NF-kB p65 Ser-536 and p38 MAPK Thr-180/Tyr-182 expression. All these proteins are described as involved in an alternative pathway that allows STAT3 Ser727 to exert a pro-survival effect thorough the regulation of mitochondrial activity. CONCLUSIONS The analysis of JAK2 and STAT3 expression, activation and inhibition lets us to highlight the importance of JAK2/STAT3 axis in the maintenance of 3 different survival pathways in CLL B cells. Furthermore, the correlation we demonstrated with clinical outcome of patients and the strengthening of Ibrutinib effect when we targeted this axis could represent a starting point for the development of new therapeutic strategies in CLL. Disclosures Trentin: Abbvie: Honoraria; Gilead: Research Funding; Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees.
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- 2018
39. Detection of Myocardial Iron Overload with Magnetic Resonance By Native T1 and T2* Mapping Using a Segmental Approach
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Daniele De Marchi, F. Mehtap Pasin, Laura Pistoia, Nicola Martini, Alessia Pepe, Antonella Massa, Vincenzo Positano, Roberto Sarli, Mauro Caini, Antonella Meloni, Aurelio Maggio, Simona Bulgarelli, Gaetano Roccamo, Piera Giovangrossi, and Andrea Barison
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education.field_of_study ,medicine.diagnostic_test ,business.industry ,Thalassemia ,Immunology ,Population ,Myocardial iron ,Magnetic resonance imaging ,Cell Biology ,Hematology ,Gold standard (test) ,medicine.disease ,Biochemistry ,Correlation ,medicine.anatomical_structure ,Fibrosis ,Ventricle ,medicine ,Nuclear medicine ,business ,education - Abstract
Introduction. T2* measurement of myocardial iron overload (MIO) is presently the gold standard for monitoring and tailoring the chelation in thalassemia patients. Native T1 mapping has been proposed also for the MIO quantification because it is known that iron can reduce native T1 values. No data are available in literature comparing T1 and T2* mapping using a segmental approach including the whole left ventricle. The goal of our study was to assess the relationship between T1 and T2* values using a segmental approach. Methods. 29 patients with hemoglopinopathies (18 females, 45.39±13.49 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered. Native T1 and T2* images were acquired, respectively, with the Modified Look-Locker Inversion recovery (MOLLI) and with the multi-echo gradient-echo techniques. Three parallel short-axis views (basal, medium and apical) of the left ventricle (LV) were acquired with ECG-gating. The myocardial T1 and T2* distribution was mapped into a 16-segment LV model, according to the AHA/ACC model. The lower limit of normal for each segment was established as mean±2 standard deviations on data acquired on 14 healthy volunteers. In 25 patients also post-contrastografic images were acquired. Results. T1 images showed more pronounced motion artifacts and lower contrast-to-noise-ratio, determining the exclusion of 18/464 segments. No segments were excluded by T2* mapping. So, globally, 446 segmental T1 and T2* values were considered. The mean of all segmental T2* and T1 values were, respectively, 37.83±11.30 ms and 982.72±118.24 ms. Normal T2* and T1 values were found in 374 segments (83.9%) while 29 (6.5%) segments had pathologic T2* and T1 values. For 33 segments (7.4%) (13 patients) a pathologic T1 value was detected in presence of a normal T2* value. For 10 segments (2.2%) a pathologic T2* value was detected in presence of a normal T1 value. Out of the 9 patients with pathologic T2* values in presence of normal T1, in 7 patients post-contrastografic images were acquired; in all segments with pathologic T2* value macroscopic fibrosis by late gadolinium enhancement technique and/or microscopic fibrosis by T1 mapping were found. The relation between segmental T1 and T2* values is shown in the figure. For patients with pathologic segmental T2* values there was a linear relationship between T1 and T2* values (R=0.735, P Conclusion. T2* and T1 mapping showed a good correlation in identifying iron by a segmental approach. However, we found a scatter between results. In 9 patients T1 mapping was not able to detect iron probably due to the presence of macroscopic and/or microscopic fibrosis that it is known to increase the native T1 . Conversely, in 13 patients T1 mapping seems to be more sensitive than T2* (sensitive to different iron chemistry or error measurements?). Further studies on larger population and correlation with clinical outcome are need. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.
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- 2018
40. Targeting Ras-Signalling Pathway to Strike Hsf1 and Induce Apoptosis in Chronic Lymphocytic Leukemia
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Livio Trentin, Andrea Visentin, Monica Facco, Emanuele Favero, Filippo Severin, Gianpietro Semenzato, Veronica Martini, Flavia Raggi, Federica Frezzato, and Valentina Trimarco
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business.industry ,Chronic lymphocytic leukemia ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Hedgehog signaling pathway ,Apoptosis ,medicine ,Cancer research ,Signal transduction ,Annexin A5 ,Idelalisib ,HSF1 ,business ,Transcription factor - Abstract
INTRODUCTION The Heat Shock Protein of 70kDa (HSP70) and its transcription factor, the Heat Shock Factor 1 (HSF1), are two cytoprotective molecules that we found overexpressed and correlated to poor prognosis in Chronic Lymphocytic Leukemia (CLL) B cells. We focused on RAS-signalling pathways, which involve proteins known to regulate HSF1 activity, such as RAS/RAF/MEK/ERK and RAS/PI3K/AKT. Taking advantage from a previous RPPA analysis (Frezzato et al., 2016), we already developed a model according to which patients with high HSP70 protein levels are characterized by the activation of RAS/PI3K/AKT pathway, while patients with low levels of HSP70 have the RAS/RAF/MEK/ERK pathway activated. The dissection of these aberrant pathways in CLL would help in providing new information on the pathobiology of CLL B cells, in order to define innovative prognostic factors and/or new therapeutic targets. METHODS Freshly isolated leukemic B cells from 20 therapy-free CLL patients were cultured in RPMI 1640 supplemented with antibiotics and 2% FBS and treated with: 10, 20 and 30µM Pterostilbene, a natural analogue of Resveratrol, which upregulates ERK and downmodulates AKT with the final effect of inhibiting HSF1 activity. Apoptosis was evaluated after 24 hours by Annexin V/Propidium iodide flow cytometry test and by the presence of cleaved PARP in Western blotting (WB). HSP70 and HSF1 expression levels were evaluated by WB analysis in leukemic B cells after in vitro and in vivo inhibition with anti-PI3K. RESULTS We previously found that molecules acting as Resveratrol on RAS signaling pathways (inhibiting HSF1 by upregulating ERK and downmodulating AKT), induce apoptosis of CLL B cells in a dose-dependent manner. Particularly, we already observed apoptosis after treatment with Triacetyl Resveratrol and Honokiol. We recently extended our preliminary data on Pterostilbene to a large cohort of patients, obtaining the following results starting from 10µM to 20µM and 30µM: 63.50 ± 14.47%, 48.50 ± 21.59% and 24.88 ± 22.03% of living cells vs untreated cells, 74.63 ± 11.77% respectively, with p value p CONCLUSIONS Our preliminary data suggest a pivotal role for HSP70 and HSF1 in CLL B cell protection against apoptosis. The dissection of RAS pathways in CLL and, in particular, the studies on their effect on the regulation of HSF1/HSP70 axis, are essential to understand the mechanisms that sustain the leukemic clone survival. The alternative and innovative approach we are developing to downmodulate HSP70 by targeting upstream-signalling molecules, will reduce the unpredictable off-target effects caused by the direct inhibition of the ubiquitous HSP70 protein and may contribute to find innovative targets for new therapeutic strategies for CLL. Disclosures Visentin: janssen: Consultancy, Honoraria. Trentin:Abbvie: Honoraria; Janssen: Research Funding; Gilead: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees.
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- 2018
41. Calcium Mobilization in Unfavorable-Prognosis Chronic Lymphocytic Leukemia Patients Mediates Focal Adhesion Kinase (FAK) Cleavage, Thereby Its Activation
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Stefano Pravato, Veronica Martini, Francesco Piazza, Livio Trentin, Monica Facco, Gianpietro Semenzato, Marco Piccoli, Federica Frezzato, Andrea Visentin, Filippo Severin, Edoardo Scomazzon, Flavia Raggi, and Silvia Imbergamo
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business.industry ,Chronic lymphocytic leukemia ,Immunology ,breakpoint cluster region ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Focal adhesion ,Leukemia ,LYN ,medicine ,Cancer research ,Annexin A5 ,Signal transduction ,Cell adhesion ,business - Abstract
INTRODUCTION Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in the western world and is characterized by the accumulation of monoclonal B cells, due to both increased proliferation and apoptosis resistance. Although in the last years with the introduction of new kinase inhibitors blocking the pathways mediated by B-cell receptor (BCR) signaling we got an astonishing progress in the comprehension and treatment of this disease, CLL is still an incurable disease and many characteristics of its pathogenesis still remain unclear. Signaling events downstream the BCR engagement are central for the progression of CLL. Focal Adhesion Kinase (FAK), one of the primary enzyme involved in the engagement of integrins and assembly of focal adhesions, plays a major role in cellular adhesion and metastasis of various cancers, being regulated by Calcium (Ca2+) flux and by Src-kinases (e.g. Lyn) through a Calpain-dependent manner following BCR triggering. FAK has been demonstrated to be over-expressed in many human cancers but a down-modulation of its expression has also been reported. Studies concerning FAK expression in CLL are lacking in the literature. However, since an interaction of FAK with molecules implicated in BCR signal transduction, such as the Src-kinase Lyn, has been demonstrated we hypothesize that this kinase could have a key role in CLL pathogenesis. METHODS FAK expression was analyzed in B-lymphocytes from 107 CLL patients and 10 healthy subjects by Western blotting (WB) and the obtained expression data were correlated with the clinical features of the patients. In 25 out of 107 patients studied, surface IgM and IgD expression has been evaluated by flow cytometry (FC). For Ca2+ mobilization assessment, 1x107 cells were incubated with 4μM Fluo-4-AM at 37°C for 30min and then analyzed by FC; after 30s of baseline acquisition, α-IgM F(ab')2 and α-IgD F(ab')2 (10μg/ml) were added and fluorescence intensity was recorded for 5min. Ionomycin was added as positive control. Phosphorylation at Tyr397 was assessed with a specific antibody. Leukemic B cells from patients were treated in vitro with 5μM Defactinib (FAK inhibitor) and the apoptosis induction was evaluated by Annexin V/Propidium Iodide flow cytometry test and by the presence of cleaved PARP by WB. RESULTS By WB analyses we demonstrated a slightly significant difference in FAK expression between patients and controls (p CONCLUSIONS We herein propose that full length-FAK down-modulation could be considered as a new marker of unfavorable prognosis. In our model, poor prognosis CLL patients (particularly IGHV unmutated ones) presenting Ca2+ mobilization, are more prone to activate Calpain, which in turn activates FAK. Together with data from the literature, our results suggest that CLL cells missing the full length-FAK, not only are unaffected by the lack of it, but they rather present a cleaved/activated form of FAK that could favor cell migration and metastatic invasion. Moreover, since Defactinib can induce apoptosis in CLL cells, should these data be confirmed by in vivo studies, this FAK inhibitor could represent a new therapeutic approach for CLL. Disclosures Trentin: Gilead: Research Funding; Abbvie: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding.
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- 2018
42. Protective Role Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukemia: FOCUS on Subcutaneous Immunoglobulin Formulations
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Francesca Romana Mauro, Robin Foà, Stefano Pravato, Serena Rosati, Edoardo Scomazzon, Silvia Imbergamo, Flavia Raggi, Veronica Martini, Federica Frezzato, Gianpietro Semenzato, Livio Trentin, Filippo Severin, and Andrea Visentin
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medicine.medical_specialty ,Immunology ,Population ,030226 pharmacology & pharmacy ,Biochemistry ,Hypogammaglobulinemia ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chemoimmunotherapy ,hemic and lymphatic diseases ,Internal medicine ,medicine ,education ,Adverse effect ,education.field_of_study ,business.industry ,Venetoclax ,Cell Biology ,Hematology ,medicine.disease ,Discontinuation ,chemistry ,030220 oncology & carcinogenesis ,Concomitant ,Ibrutinib ,business - Abstract
INTRODUCTION. Secondary antibody deficiency is a common complication in chronic lymphocytic leukemia (CLL) that could be present at diagnosis or can be acquired during the follow-up due to CLL progression, perturbation of non-neoplastic immune system and chemoimmunotherapy. Despite new and active target therapies a significant amount of CLL patients still develops severe and life-threatening infections. Intravenous immunoglobulin (IG) (IVIG) replacement therapy (IGRT) has been proven to be an effective supportive treatment in patients with primary and secondary antibody deficiency such as CLL. Subcutaneous immunoglobulin (SCIG) is a new valid treatment option that allows patients self-administration without access to the clinic which proved to be as effective as IVIG in primary immunodeficiencies. However, the activity SCIG is CLL patients with IG defect has been little investigated. The aim of this study was to retrospectively evaluate IG levels, infection rate and safety of patients treated with SCIG as compared to those managed with IVIG. METHODS. Inclusion criteria were: diagnosis of CLL according to iwCLL guideline, age >18 years, received at least 1 IVIG or SCIG infusion. IGRT was started according to hospital policies in patient with severe symptomatic hypogammaglobulinemia. The physician was responsible for the choice between IGRT formulations (the first patient received SCIG since Nov 2008). IG levels (IgG, IgA and IgM) were recorded within 3 months before starting IGRT (baseline), after 6 months and within three months from the last available follow-up. Continuous variables were compared with Wilcoxon's tests while categorical variables with Fisher's exact or Chi-square tests when appropriate. Time to IGRT discontinuation was calculated from the beginning IGRT to death or discontinuation (event) or last available follow-up /(censored). RESULTS. We gathered data from 116 CLL patients followed in 2 hematology centers who received IGRT: 63% were male, the median age at diagnosis was 58 years, 77 were at Binet A stage, 48% and 16% were unmutated IGHV and harbor TP53 abnormalities, respectively. 91% received at least one therapies, the median numbers of treatments were 3 (range 0-9) and 36% died during the follow-up due to infections in 22 cases, CLL progression in 5, Richter transformation in 6 patients and 9 other causes such as second cancers or major bleedings. Forty-nine patients received IVIG and 88 SCIG (41 the 20% formulation and 47 the 16% drugs). Despite similar basal and +6 months IgG levels, patients treated with SCIG achieved significant higher serum IgG at last available follow-up (3.99, 5.67 and 5.4 g/L vs 3.89, 6.07 and 6.22 g/L for IVIG and SCIG, p=0.0009). Both IgA and IgM levels remained stable during replacement therapy. While the number of grade 3-4 infections remain stable during IVIG (both 80% before and after IVIG), they decrease with SCIG (88% vs 64%, p Adverse events during SCIG infusions occurred in 11% of subjects, most commonly skin reaction and pruritus. They were mild, limited to the site of infusion and easily to manage. Bruising did not increase during concomitant treatment of SCIG and ibrutinib. After a median duration of IGRT of 3.7 years (4.7 for IVIG and 3.1 for SCIG) 71% of subjects managed with IGEV discontinued therapy as compared to 36% of SC formulation (p CONCLUSIONS. In this study we described the clinical and biological characteristics of the bigger population with CLL and secondary hypogammaglobulinemia receiving IGRT. We demonstrated that SCIG are well tolerated, non-inferior to IVIG, they also allow to reach higher IgG through levels and to decrease the incidence of severe infections even during continuous CLL therapies. Disclosures Visentin: janssen: Consultancy, Honoraria. Mauro:abbvie: Other: board member; janssen: Other: board member. Foà:ROCHE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; NOVARTIS: Speakers Bureau. Trentin:Gilead: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Janssen: Research Funding.
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- 2018
43. An Innovative Integrated Capacity Building Project for Stem Cell Transplantation in the Southern Lazio Region
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Francesca Saltarelli, Roberta Sala, Ignazio Majolino, Alessandro Andriani, Vincenzo Iaconianni, Vincenza Martini, and Laura De Padua
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Transplantation ,Geography ,Lazio region ,Immunology ,Capacity building ,Cell Biology ,Hematology ,Stem cell ,Biochemistry ,Environmental planning - Abstract
Autologous stem cell transplantation (ASCT) is a standard treatment for many hematological disorders. Since ASCT needs technical and professional skills, a start-up process should imply the application of a specific methodology to reduce time and costs, and to optimize the results. We describe here an innovative and integrated process leading to the start-up of a transplant activity in the Hematology Unit of the general hospital of Frosinone, southern Lazio, Italy. The method had previously been employed successfully by one of us in a critical context (Mediterr J Hematol Infect Dis. 2017 Apr 15;9). Since 1996, the Hematology Unit in Frosinone gained experience in treating malignant and non malignant disorders, but HSCT could not be performed so patients were referred to other institutions in the country with remarkable costs and discomfort. The innovative aspect of our project is the application of a capacity building methodology aimed at establishing a quality system prior to the initiation of the clinical transplant activity. Capacity building is a continuous process addressed to individuals, organizations and institutions aiming at developing abilities and achieve objectives. A preliminary step was to check sustainability,ie whether the institution was suitable to support an ASCT activity, and to assess the level of expertise of the medical and nurse staff involved in the process. In fact, our Hospital was lacking some of the facilities required to perform ASCT, such as apheresis and stem cell manipulation. To overcome the obstacle, an agreement with the close Latina Hospital that has consolidated experience in ASCT was established, gaining access to their facilities and expertise. In June 2018 we held a first training course addressed to physicians and nurses that covered different aspects of ASCT. A scientific advisor led the process of editing clinical protocols and procedures. Simultaneously a quality system was built based on clinical guidelines that follow the international FACT-JACIE standards. In this phase, the document management system, the outcome indicators and the main rules of the transplant program were created. In order to improve the educational program we planned a second training phase based on on-site coaching. To better accomplish the task, physicians and nurses are now asked to highlight the practical aspects of the process that require further development trough a simple questionnaire. During this second training phase, selected physicians and nurses with experience in transplantation will undertake an open discussion about the aspects requiring further evaluation. The goal is to perform our first autologous transplant within four months since the start of the project. We believe that the capacity building process through on-site training and coaching represents an innovative effective method for developing autonomous skills needed to conduct a sustainable HSCT program. Disclosures No relevant conflicts of interest to declare.
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- 2018
44. Dual or Single Hepatitis B and C Virus Infections in Childhood Cancer Survivors: Long-Term Follow-Up and Effect of Interferon Treatment
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Utili, Riccardo, Zampino, Rosa, Bellopede, Pasquale, Marracino, Marta, Ragone, Enrico, Adinolfi, Luigi Elio, Ruggiero, Giuseppe, Capasso, Maria, Indolfi, Paolo, Casale, Fiorina, Martini, Adele, and Di Tullio, Maria Teresa
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- 1999
- Full Text
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45. Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia
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Anna Cabrelle, Renato Zambello, Veronica Martini, Federica Frezzato, Antonella Teramo, Elisa Boscaro, Livio Trentin, Francesco Piazza, Cristina Gattazzo, Elisa Ave, Valentina Trimarco, Francesca Passeri, Albana Lico, Monica Facco, Gianpietro Semenzato, and Giulia Tasca
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Male ,STAT3 Transcription Factor ,Large granular lymphocytic leukemia ,Immunology ,Population ,Suppressor of Cytokine Signaling Proteins ,Biochemistry ,chemistry.chemical_compound ,medicine ,Humans ,SOCS3 ,Phosphorylation ,STAT3 ,education ,Cells, Cultured ,Aged ,Janus Kinases ,education.field_of_study ,biology ,JAK-STAT signaling pathway ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Demethylating agent ,Leukemia, Large Granular Lymphocytic ,STAT Transcription Factors ,Leukemia ,chemistry ,Suppressor of Cytokine Signaling 3 Protein ,Mutation ,Cancer research ,biology.protein ,Female ,Janus kinase ,Signal Transduction - Abstract
The JAK/STAT pathway is altered in T-cell large granular lymphocytic leukemia. In all patients, leukemic LGLs display upregulation of phosphorylated STAT3 (P-STAT3) that activates expression of many antiapoptotic genes. To investigate the mechanisms maintaining STAT3 aberrantly phosphorylated using transcriptional protein and functional assays, we analyzed interleukin (IL)-6 and suppressor of cytokine signaling-3 (SOCS3), 2 key factors of the JAK/STAT pathway that induce and inhibit STAT3 activation, respectively. We showed that IL-6 was highly expressed and released by the patients' peripheral blood LGL-depleted population, accounting for a trans-signaling process. By neutralizing IL-6 or its specific receptor with specific antibodies, a significant reduction of P-STAT3 levels and, consequently, LGL survival was demonstrated. In addition, we found that SOCS3 was down-modulated in LGL and unresponsive to IL-6 stimulation. By treating neoplastic LGLs with a demethylating agent, IL-6-mediated SOCS3 expression was restored with consequent P-STAT3 and myeloid cell leukemia-1 down-modulation. Methylation in the SOCS3 promoter was not detectable, suggesting that an epigenetic inhibition mechanism occurs at a different site. Our data indicate that loss of the inhibitor SOCS3 cooperates with IL-6 to maintain JAK/STAT pathway activation, thus contributing to leukemic LGL survival, and suggest a role of demethylating agents in the treatment of this disorder.
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- 2013
46. Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors
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Manola Comar, Fernanda Martini, Elisa Mazzoni, Cecilia Pancaldi, Mauro Tognon, Valentina Corazzari, Stefania Maniero, Pancaldi, C, Corazzari, V, Maniero, S, Mazzoni, E, Comar, Manola, Martini, F, and Tognon, M.
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tumors ,Chronic lymphocytic leukemia ,Merkel cell polyomavirus ,Buffy coat ,Polymerase Chain Reaction ,Biochemistry ,law.invention ,law ,Prevalence ,Polymerase chain reaction ,Expressed Sequence Tags ,Hematology ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Merkel cell carcinoma ,Middle Aged ,Viral Load ,Amplicon ,prevalence in population ,Italy ,Antibody ,Databases, Nucleic Acid ,Polyomavirus ,Adult ,tumor ,medicine.medical_specialty ,Molecular Sequence Data ,Immunology ,Young Adult ,infection ,buffy coat ,blood donor ,Internal medicine ,medicine ,Humans ,Aged ,Polyomavirus Infections ,Base Sequence ,Merkel cell Viru ,Sequence Analysis, DNA ,Cell Biology ,biology.organism_classification ,medicine.disease ,Virology ,Merkel cell Virus ,Carcinoma, Merkel Cell ,Tumor Virus Infections ,Blood Buffy Coat ,DNA, Viral ,biology.protein ,Sequence Alignment - Abstract
Merkel cell polyomavirus (MCPyV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy blood donors. This high seroprevalence suggests that MCPyV infection is widespread in humans. In our study, buffy coats, which were examined for MCPyV DNA Tag sequences, showed a prevalence of 22%. Viral DNA load was revealed in blood samples from 10 to 100 molecules/100 000 cells. DNA sequencing confirmed that polymerase chain reaction amplicons belong to the MCPyV strain, MKL-1. To interpret the putative role of MCPyV in chronic lymphocytic leukemia, we may infer that, during a long period of viral persistence in blood cells, this DNA tumor virus may generate mutants, which are able to participate as cofactors in the multistep process of cell transformation.
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- 2011
47. Dual or Single Hepatitis B and C Virus Infections in Childhood Cancer Survivors: Long-Term Follow-Up and Effect of Interferon Treatment
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Enrico Ragone, Paolo Indolfi, Maria Teresa Di Tullio, Maria Capasso, Giuseppe Ruggiero, Riccardo Utili, Adele Martini, Fiorina Casale, Marta Marracino, Pasquale Bellopede, Rosa Zampino, L. E. Adinolfi, Utili, Riccardo, Zampino, Rosa, Bellopede, P, Marracino, M, Ragone, E, Adinolfi, Luigi Elio, Ruggiero, G, Capasso, M, Indolfi, P, Casale, Fiorina, Martini, A, and DI TULLIO, Mt
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Male ,HBsAg ,medicine.medical_specialty ,Cirrhosis ,Adolescent ,Hepatitis C virus ,Immunology ,medicine.disease_cause ,Antiviral Agents ,Biochemistry ,Gastroenterology ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Prospective Studies ,Seroconversion ,Child ,Hepatitis B virus ,Hepatitis ,business.industry ,Infant ,Interferon-alpha ,virus diseases ,Cell Biology ,Hematology ,Hepatitis B ,medicine.disease ,Hepatitis C ,digestive system diseases ,HBeAg ,Child, Preschool ,Female ,business ,Follow-Up Studies - Abstract
We conducted a long-term prospective study of 89 cancer survivor children who had acquired hepatitis B virus (HBV) and/or hepatitis C virus (HCV) during treatment for neoplasia, the aim being to evaluate the natural history of the diseases and the effect of interferon (IFN) treatment. Patients were followed up for a median period of 13 years (range, 8 to 20); 46 were infected by HBV, 11 by HCV, and 32 coinfected by HBV and HCV. A spontaneous clearance of hepatitis B surface antigen (HBsAg) occurred more frequently in coinfected patients (19%) than in the HBV-infected (2%; P = .004), with an annual seroconversion rate of 2.1% and 0.2%, respectively (P= .008). Loss of hepatitis Be antigen (HBeAg) occurred in 44% of coinfected and in 28% of HBV-infected patients. Clearance of serum HCV-RNA was observed in 34% and 9%, respectively, of coinfected and HCV-infected patients. Seventeen HBV-infected, 4 HCV-infected, and 16 coinfected patients received -IFN treatment. In the HBV group, 6 patients (35%) cleared serum HBV DNA and seroconverted to anti-HBe; in the HCV-group, none cleared HCV-RNA. In the coinfected group, 1 patient cleared both HBV DNA and HCV-RNA, 6 patients cleared serum HCV-RNA alone, and 1 only HBV DNA and HBeAg. Overall, the diseases showed a mild histological course with no evidence of liver cirrhosis. A reciprocal interference on viral replication between HBV and HCV may occur in coinfected patients. Treatment seems to be effective for selected cases and is justified in view of the uncertain prognosis of the disease in these patients.
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- 1999
48. CALR mutations in patients with essential thrombocythemia diagnosed in childhood and adolescence
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Deborah Marzella, Marica Laurino, Luigi Maria Larocca, Fiorina Giona, Daniela Diverio, Luciana Teofili, Giovanna Palumbo, Sara Capodimonti, Maurizio Martini, and Robin Foà
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Adult ,Male ,MYELOPROLIFERATIVE NEOPLASMS ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Immunology ,Biochemistry ,Young Adult ,medicine ,Humans ,In patient ,Young adult ,Child ,Myelofibrosis ,Adult patients ,business.industry ,Essential thrombocythemia ,Age Factors ,Infant ,Calr gene ,Cell Biology ,Hematology ,medicine.disease ,Settore MED/15 - MALATTIE DEL SANGUE ,Child, Preschool ,Mutation ,thrombocythemia diagnosed in childhoodand adolescence ,Female ,Calreticulin ,business ,Thrombocythemia, Essential - Abstract
To the editor: After the recent discovery of various mutations of the CALR gene
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- 2014
49. Different STAT-3 and STAT-5 phosphorylation discriminates among Ph-negative chronic myeloproliferative diseases and is independent of the V617F JAK-2 mutation
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Francesco Guidi, Luigi Maria Larocca, Maurizio Martini, Luciana Teofili, Sergio Storti, Tonia Cenci, Lorenza Torti, Giovanna Petrucci, and Giuseppe Leone
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STAT3 Transcription Factor ,medicine.medical_specialty ,jak-2 mutation ,Immunology ,Biology ,Biochemistry ,Diagnosis, Differential ,Polycythemia vera ,hemic and lymphatic diseases ,Internal medicine ,STAT5 Transcription Factor ,medicine ,Humans ,Point Mutation ,Stat 3 ,Philadelphia Chromosome ,Stat 5 ,Phosphorylation ,Myelofibrosis ,Polycythemia Vera ,Myeloproliferative Disorders ,Janus kinase 2 ,Hematology ,Settore MED/08 - ANATOMIA PATOLOGICA ,Thrombocytosis ,medicine.diagnostic_test ,Essential thrombocythemia ,Bone Marrow Examination ,Cell Biology ,Janus Kinase 2 ,medicine.disease ,Bone marrow examination ,medicine.anatomical_structure ,Primary Myelofibrosis ,biology.protein ,Cancer research ,Bone marrow ,Thrombocythemia, Essential - Abstract
The V617F JAK2 mutation reported in Ph-negative myeloproliferative diseases (MPDs) induces the constitutive activation of JAK2, which produces an increased phosphorylation of signal transducer activator of transcription (STAT). In this study, we have analyzed a series of 114 patients (54 with polycythemia vera [PV], 44 with essential thrombocythemia [ET], 12 with idiopathic myelofibrosis [IM], and 4 with myelofibrosis secondary to MPD) for the expression pattern of phosphorylated STAT-3 and STAT-5 (pSTAT-3 and pSTAT-5, respectively) by immunostaining bone marrow biopsies. We found 3 specific patterns of pSTAT-3 and pSTAT-5 expression, significantly different from the normal staining pattern: uniformly increased pSTAT-3 and pSTAT-5 expression in PV, increased pSTAT-3 and reduced pSTAT-5 expression in ET, and uniformly reduced pSTAT-3 and pSTAT-5 expression in IM. A moderate increase of pSTAT-3 and pSTAT-5 expression was observed in secondary forms of erythrocytosis and thrombocytosis. In all evaluated MPDs, the pSTAT-5 and pSTAT-3 expression pattern was not influenced by the presence of V617F JAK2 mutation. These findings underline the importance of bone marrow histology in the differential diagnosis of Ph-negative MPD and support the hypothesis that V617F mutation simply contributes with other molecular defects in allowing the PV, ET, or IM phenotype to emerge.
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- 2007
50. Inhibition of JAK2/STAT3 Pathway Leads to Apoptosis in Chronic Lymphocytic Leukemia Cells
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Severin, Filippo, primary, Frezzato, Federica, additional, Martini, Veronica, additional, Raggi, Flavia, additional, Trimarco, Valentina, additional, Martinello, Leonardo, additional, Visentin, Andrea, additional, Facco, Monica, additional, Semenzato, Gianpietro, additional, and Trentin, Livio, additional
- Published
- 2016
- Full Text
- View/download PDF
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