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

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

doi:10.1371/journal.pone.0048485

Abstract

BackgroundPatients 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.ResultsChronic 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-.ConclusionsThis 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.

Highlights

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
Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of mature, monoclonal B lymphocytes in the blood, bone marrow (BM) and secondary lymphoid tissues [1]
Recent data from our group and others, suggest that patients with CLL and 13q deletion as the only Fluorescent in situ hybridization (FISH) abnormality could have a different outcome depending on the number of cells displaying this aberration [11,12,13]

Summary

Introduction

Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of mature, monoclonal B lymphocytes in the blood, bone marrow (BM) and secondary lymphoid tissues [1]. The clinical course ranges from an indolent disorder with a normal lifespan to a rapidly progressive disease leading to death [2,3]. The variable clinical course of CLL is driven, at least in part, by the immunogenetic and molecular heterogeneity of the disease [4,5]. Fluorescent in situ hybridization (FISH) can detect genomic abnormalities in more than 80% of CLL cases and the genetic subtypes of CLL show different biological and clinical features [5]. 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. The goal of the study was to analyze the genetic profile of 13q-H patients

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Conclusion