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

• Published in: PloS one Vol. 7; no. 11; p. e48485
• Main Authors: Rodríguez, Ana Eugenia, Hernández, Jose Ángel, Benito, Rocío, Gutiérrez, Norma C., García, Juan Luis, Hernández-Sánchez, María, Risueño, Alberto, Sarasquete, M. Eugenia, Fermiñán, Encarna, Fisac, Rosa, de Coca, Alfonso García, Martín-Núñez, Guillermo, de las Heras, Natalia, Recio, Isabel, Gutiérrez, Oliver, De Las Rivas, Javier, González, Marcos, Hernández-Rivas, Jesús M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.11.2012; Public Library of Science (PLoS)
• Subjects: Aberration; Adult; Aged; Aged, 80 and over; Alleles; Analysis; Apoptosis; B cells; Biology; Case-Control Studies; Cell survival; Chromosome 13; Chromosome Deletion; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 17; Chronic lymphocytic leukemia; Clonal deletion; Cluster Analysis; Deregulation; Female; Flow cytometry; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genes; Heterogeneity; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Lymphatic leukemia; Lymphocyte receptors; Male; Medical prognosis; Medicine; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Mutation; NF-κB protein; Patients; Ribonucleic acid; RNA; Signal Transduction; Signaling; Studies; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048485

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. A total of 102 samples were studied, 32 of which served as a validation cohort and five were healthy donors. 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-. 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.