The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia

Cancer Cell. 2010 Jan 19;17(1):28-40. doi: 10.1016/j.ccr.2009.11.019. Epub 2010 Jan 7.

Abstract

Chronic lymphocytic leukemia (CLL) is a malignancy of B cells of unknown etiology. Deletions of the chromosomal region 13q14 are commonly associated with CLL, with monoclonal B cell lymphocytosis (MBL), which occasionally precedes CLL, and with aggressive lymphoma, suggesting that this region contains a tumor-suppressor gene. Here, we demonstrate that deletion in mice of the 13q14-minimal deleted region (MDR), which encodes the DLEU2/miR-15a/16-1 cluster, causes development of indolent B cell-autonomous, clonal lymphoproliferative disorders, recapitulating the spectrum of CLL-associated phenotypes observed in humans. miR-15a/16-1-deletion accelerates the proliferation of both human and mouse B cells by modulating the expression of genes controlling cell-cycle progression. These results define the role of 13q14 deletions in the pathogenesis of CLL.

MeSH terms

  • Animals
  • B-Lymphocytes / pathology*
  • Blotting, Southern
  • Cell Cycle / genetics
  • Cell Proliferation
  • Gene Deletion
  • Gene Expression Regulation
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Multigene Family
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MicroRNAs
  • Mirn15a microRNA, mouse
  • Mirn16 microRNA, mouse
  • Proteins
  • Dleu2 protein, mouse

Associated data

  • GEO/GSE18866