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oai:docta.ucm.es:20.500.14352/932972025-09-02T12:19:23Zcom_20.500.14352_14col_20.500.14352_15

A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia Hernández Rivas, José Ángel Hernández Sánchez, María Rodríguez Vicente, Ana Eugenia Grossmann, Vera Collado, Rosa Heras, Cecilia Puiggros, Anna Martín, Ana África Puig, Noemí Benito, Rocío Robledo, Cristina Delgado, Julio González, Teresa Queizán, José Antonio Galende, Josefina Fuente, Ignacio De La Martín-Núñez, Guillermo Alonso, José María Abrisqueta, Pau Luño, Elisa Marugán, Isabel González Gascón, Isabel Bosch, Francesc Kohlmann, Alexander González, Marcos Espinet, Blanca Hernández Rivas, Jesús María Spencer B. Gibson Ciencias Biomédicas 24 Ciencias de la Vida To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence in situ hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ≥40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q) (11q-L) (P<0.0001). In the multivariate analysis, only the presence of 11q-L, mutated IGHV status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached (P = 0.008). The absence of splenomegaly (P = 0.02), low LDH (P = 0.018) or β2M (P = 0.006), and the presence of 11q-L (P = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the ATM, TP53, NOTCH1, SF3B1, MYD88, FBXW7, XPO1 and BIRC3 genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q- showed mutations and fewer patients with low frequencies of 11q- had mutations among genes examined (50% vs 94.1%, P = 0.023). In summary, CLL patients with <40% of 11q- had a long TFT and OS that could be associated with the presence of fewer mutated genes. Instituto de Salud Carlos III European Commission Fundación Manuel Solórzano Caja Burgos Fundación Española de Hematología y Hemoterapia Red Temática de Investigación Cooperativa en Cáncer Ministerio de Economía y Competitividad (España) Junta de Castilla y León MLL Munich AstraZeneca Depto. de Bioquímica y Biología Molecular Fac. de Farmacia TRUE pub 2024-01-16T10:14:19Z 2024-01-16T10:14:19Z 2015 journal article VoR https://hdl.handle.net/20.500.14352/93297 XXXX-XXXX 10.1371/journal.pone.0143073 1932-6203 eng info:eu-repo/grantAgreement/355/A/09 info:eu-repo/grantAgreement/GRS/1172/A15 info:eu-repo/grantAgreement/RD12/0036/0069 info:eu-repo/grantAgreement/RD12/0036/0044 info:eu-repo/grantAgreement/306242-NGS-PTL Hernández JÁ, Hernández-Sánchez M, Rodríguez-Vicente AE, Grossmann V, Collado R, Heras C, et al. A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia. PLoS ONE 2015;10:e0143073. https://doi.org/10.1371/journal.pone.0143073. Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf Public Library of Science