RT Journal Article
T1 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
A1 Hernández Rivas, José Ángel
A1 Hernández Sánchez, María
A1 Rodríguez-Vicente, Ana Eugenia
A1 Grossmann, Vera
A1 Collado, Rosa
A1 Heras, Cecilia
A1 Puiggros, Anna
A1 Martín, Ana África
A1 Puig, Noemí
A1 Benito, Rocío
A1 Robledo, Cristina
A1 Delgado, Julio
A1 González, Teresa
A1 Queizán, José Antonio
A1 Galende, Josefina
A1 Fuente, Ignacio de la
A1 Martín-Núñez, Guillermo
A1 Alonso, José María
A1 Abrisqueta, Pau
A1 Luño, Elisa
A1 Marugán, Isabel
A1 González-Gascón, Isabel
A1 Bosch, Francesc
A1 Kohlmann, Alexander
A1 González, Marcos
A1 Espinet, Blanca
A1 Hernández-Rivas, Jesús María
A2 Spencer B. Gibson, 
AB 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.
PB Public Library of Science
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/93297
UL https://hdl.handle.net/20.500.14352/93297
LA eng
NO 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.
NO Instituto de Salud Carlos III
NO European Commission
NO Fundación Manuel Solórzano
NO Caja Burgos
NO Fundación Española de Hematología y Hemoterapia
NO Red Temática de Investigación Cooperativa en Cáncer
NO Ministerio de Economía y Competitividad (España)
NO Junta de Castilla y León
NO MLL Munich
NO AstraZeneca
DS Docta Complutense
RD 22 jul 2024