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Title:	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
Authors:	Hernández, José Ángel; Hernández-Sánchez, María; Rodríguez-Vicente, Ana Eugenia; Benito, Rocío; Robledo, Cristina; Kohlmann, Alexander; González, Marcos ; Espinet, Blanca; Hernández, Jesús M.
Issue Date:	2015
Publisher:	Public Library of Science
Citation:	PLoS ONE 10(11): e0143073 (2015)
Abstract:	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 11qshowed 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 11qhad a long TFT and OS that could be associated with the presence of fewer mutated genes.
Description:	This is an open access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL):	http://dx.doi.org/10.1371/journal.pone.0143073
URI:	http://hdl.handle.net/10261/134285
DOI:	10.1371/journal.pone.0143073
Identifiers:	doi: 10.1371/journal.pone.0143073 issn: 1932-6203
Appears in Collections:	(IBMCC) Artículos