Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia

Leuk Lymphoma. 2015;56(11):3150-8. doi: 10.3109/10428194.2015.1028051. Epub 2015 May 18.

Abstract

In this study we investigated specific biological and clinical features associated with chronic lymphocytic leukemia (CLL) patients carrying stereotyped BCR subset #4 (IGHV4-34) among a prospective cohort of 462 CLL/MBL patients in early stage (Binet A). All subset #4 patients (n = 16) were characterized by the IGHV mutated gene configuration, and absence of unfavorable cytogenetic lesions, NOTCH1 or SF3B1 mutations. Gene and miRNA expression profiling evidenced that the leukemic cells of subset #4 cases showed significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC gene transcripts, as well as the upregulation of miR-497 and miR-29c. The transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, a known validated target of this miRNA. Our data identify biological characteristics associated with subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the tumor cells in CLL.

Keywords: B-cell receptor; BCL2; chronic lymphocytic leukemia; gene expression profiling; microRNA; stereotyped VH CDR.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocyte Subsets / metabolism
  • Cluster Analysis
  • Complementarity Determining Regions / genetics
  • Computational Biology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Mutation
  • Phosphoproteins / genetics
  • RNA Splicing Factors
  • Receptor, Notch1 / genetics
  • Receptors, Antigen, B-Cell / genetics*
  • Receptors, Antigen, B-Cell / metabolism
  • Reproducibility of Results
  • Ribonucleoprotein, U2 Small Nuclear / genetics
  • Transcriptome*

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • MicroRNAs
  • Phosphoproteins
  • RNA Splicing Factors
  • Receptor, Notch1
  • Receptors, Antigen, B-Cell
  • Ribonucleoprotein, U2 Small Nuclear
  • SF3B1 protein, human