Molecular Characterization of Chronic Lymphocytic Leukemia Patients with a High Number of Losses in 13q14

Rodríguez, Ana Eugenia; Hernández, Jose Ángel; Benito, Rocío; Gutiérrez, Norma; García, Juan Luis; Hernández Sánchez, María; Risueño, Alberto; Sarasquete, M. Eugenia; Fermiñán, Encarna; Fisac, Rosa; García de Coca, Alfonso; Martín-Núñez, Guillermo; Heras, Natalia de las; Recio, Isabel; Gutiérrez, Oliver; Rivas, Javier De Las; González, Marcos; Hernández-Rivas, Jesús

Molecular Characterization of Chronic Lymphocytic Leukemia Patients with a High Number of Losses in 13q14

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Official URL

https://doi.org/10.1371/journal.pone.0048485

Publication date

2012

Authors

Rodríguez, Ana Eugenia

Hernández, Jose Ángel

Benito, Rocío

Gutiérrez, Norma

García, Juan Luis

Hernández Sánchez, María

Risueño, Alberto

Sarasquete, M. Eugenia

Fermiñán, Encarna

Fisac, Rosa

Publisher

Public Library of Science

Citations

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URI

https://hdl.handle.net/20.500.14352/93345

Citation

Rodríguez AE, Hernández JÁ, Benito R, Gutiérrez NC, García JL, Hernández-Sánchez M, et al. Molecular Characterization of Chronic Lymphocytic Leukemia Patients with a High Number of Losses in 13q14. PLoS ONE 2012;7:e48485. https://doi.org/10.1371/journal.pone.0048485.

Abstract

Background Patients with chronic lymphocytic leukemia and 13q deletion as their only FISH abnormality could have a different outcome depending on the number of cells displaying this aberration. Thus, cases with a high number of 13q- cells (13q-H) had both shorter overall survival and time to first therapy. The goal of the study was to analyze the genetic profile of 13q-H patients. Design and Methods: A total of 102 samples were studied, 32 of which served as a validation cohort and five were healthy donors. Results Chronic lymphocytic leukemia patients with higher percentages of 13q- cells (>80%) showed a different level of gene expression as compared to patients with lower percentages (<80%, 13q-L). This deregulation affected genes involved in apoptosis and proliferation (BCR and NFkB signaling), leading to increased proliferation and decreased apoptosis in 13q-H patients. Deregulation of several microRNAs, such as miR-15a, miR-155, miR-29a and miR-223, was also observed in these patients. In addition, our study also suggests that the gene expression pattern of 13q-H cases could be similar to the patients with 11q- or 17p-. Conclusions This study provides new evidence regarding the heterogeneity of 13q deletion in chronic lymphocytic leukemia patients, showing that apoptosis, proliferation as well as miRNA regulation are involved in cases with higher percentages of 13q- cells.