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Sorigue M, Sancho JM, García O, Vila J, Moreno M, Ribera JM

[Mantle cell lymphoma, response to treatment and prognosis in 45 patients].

Med Clin (Barc) 5 May 2016, . Epub 5 May 2016
Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients.
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Nomdedéu JF, Puigdecanet E, Bussaglia E, Hernández JJ, Carricondo M, Estivill C, Martí-Tutusaus JM, Tormo M, Zamora L, Serrano E, Perea G, de Llano MP, García A, Sánchez-Ortega I, Ribera JM, Nonell L, Aventin A, Solé F, Brunet MS, Sierra J

Feasibility of the AML profiler (Skyline™ Array) for patient risk stratification in a multicentre trial: a preliminary comparison with the conventional approach.

Hematol Oncol 3 May 2016, . Epub 3 May 2016
Deoxyribonucleic acid microarrays allow researchers to measure mRNA levels of thousands of genes in a single experiment and could be useful for diagnostic purposes in patients with acute myeloid leukaemia (AML). We assessed the feasibility of the AML profiler (Skyline™ Array) in genetic stratification of patients with de novo AML and compared the results with those obtained using the standard cytogenetic and molecular approach. Diagnostic bone marrow from 31 consecutive de novo AML cases was used to test MLL-PTD, FLT3-ITD and TKD, NPM1 and CEBPAdm mutations. Purified RNA was used to assess RUNX1-RUNX1T1, PML-RARα and CBFβ-MYH11 rearrangements. RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD-NPM1) and BAALC and EVI1 expression. Thirty cases were successfully analysed with both methods. Five cases had FLT3-ITD. In one case, a t(8;21) was correctly detected by both methods. Four cases had inv(16); in one, the RNA quality was unsatisfactory and it was not hybridized, and in the other three, the AML profiler detected the genetic lesion - this being a rare type I translocation in one case. Two cases with acute promyelocytic leukaemia were diagnosed by both methods. Results for NPM1 mutations were concordant in all but two cases (2/11, non-ABD mutations). Analysis of costs and turnaround times showed that the AML profiler was no more expensive than the conventional molecular approach. These results suggest that the AML profiler could be useful in multicentre trials to rapidly identify patients with AML with a good prognosis. Copyright © 2016 John Wiley & Sons, Ltd.
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Baptista MJ, Hernandez-Rodriguez A, Martinez-Caceres E, Morgades M, Martinez-Picado J, Sirera G, Sancho JM, Feliu E, Ribera JM, Navarro JT

Epstein-Barr viral loads and serum free light chains levels are potential follow-up markers of HIV-related lymphomas.

Leuk. Lymphoma 28 Apr 2016, 1-3. Epub 28 Apr 2016More information
Motlló C, Ribera JM, Morgades M, Granada I, Montesinos P, Brunet S, Bergua J, Tormo M, García-Boyero R, Sarrà J, Del Potro E, Grande C, Barba P, Bernal T, Amigo ML, Grau J, Cervera J, Feliu E

Frequency and prognostic significance of t(v;11q23)/KMT2A rearrangements in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols.

Leuk. Lymphoma 27 Apr 2016, 1-8. Epub 27 Apr 2016
The karyotype is an important predictor of outcome in acute lymphoblastic leukemia (ALL). Rearrangements of the 11q23 region involving the KMT2A gene confer an unfavorable prognosis. Forty-six adult ALL patients from the PETHEMA Group treated with risk-adapted protocols, with t(v;11q23) were selected for this study. Complete response (CR) was attained in 38 patients; 25 remained in CR after consolidation. Twelve (48%) received allogeneic hematopoietic stem cell transplantation (HSCT) and 13 delayed intensification and maintenance. The 5-year CR duration probability was 37% (95% CI, 19%-55%). A trend for a longer CR duration was observed in patients undergoing HSCT vs. those receiving chemotherapy. The 5-year overall survival (OS) probability was 20% (95% CI, 5%-35%). The OS was better, albeit not significant, in patients with a MRD level <0.1% after induction (39% [95% CI, 14%-64%] vs. 13% [95% CI, 0%-36%]). Specific treatment approaches are required to improve the outcome of patients with KMT2A-rearrangements.
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Ramos F, Robledo C, Izquierdo-García FM, Suárez-Vilela D, Benito R, Fuertes M, Insunza A, Barragán E, Del Rey M, de Morales JM, Tormo M, Salido E, Zamora L, Pedro C, Sánchez-Del-Real J, Díez-Campelo M, Del Cañizo C, Sanz GF, Hernández-Rivas JM

Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis.

Oncotarget 26 Apr 2016, . Epub 26 Apr 2016
The biological and molecular events that underlie bone marrow fibrosis in patients with myelodysplastic syndromes are poorly understood, and its prognostic role in the era of the Revised International Prognostic Scoring System (IPSS-R) is not yet fully determined. We have evaluated the clinical and biological events that underlie bone marrow fibrotic changes, as well as its prognostic role, in a well-characterized prospective patient cohort (n=77) of primary MDS patients. The degree of marrow fibrosis was linked to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10, but not to other covariates including the IPSS-R score. The presence of bone marrow fibrosis grade 2 or higher was associated with the presence of mutations in cohesin complex genes (31.5% vs. 5.4%, p=0.006). By contrast, mutations in CALR, JAK2, PDGFRA, PDGFRB,and TP53 were very rare. Survival analysis showed that marrow fibrosis grade 2 or higher was a relevant significant predictor for of overall survival, and independent of age, performance status, and IPSS-R score in multivariate analysis.
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