Function of the inv(16) fusion gene CBFB-MYH11

Curr Opin Hematol. 2001 Jul;8(4):201-5. doi: 10.1097/00062752-200107000-00004.

Abstract

Inv(16)(p13q22) is associated with acute myeloid leukemia subtype M4Eo, which is characterized by the presence of myelomonocytic blasts and atypical eosinophils. This chromosomal rearrangement results in the fusion of CBFB and MYH11 genes. Mouse models indicate that the fusion gene, Cbfb-MYH11, inhibits differentiation of hematopoietic cells. Although expression of Cbfb-MYH11 is not sufficient for leukemogenesis, a combination of Cbfb-MYH11 and additional mutations can lead specifically to the development of myeloid leukemia. Normally, CBFbeta interacts with CBFalpha to form a transcriptionally active nuclear complex. In vitro studies indicate that expression of CBFB-MYH11 leads to sequestration of CBFalpha2 in the cytoplasm. It also has been shown to inhibit CBF-mediated transactivation, slow cell cycle progression, delay the apoptotic response to DNA damaging agents, and protect CBFalpha2 from degradation. The importance of these functions in vivo remains to be determined.

Publication types

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

MeSH terms

  • Animals
  • Chromosome Inversion
  • Core Binding Factor alpha Subunits
  • Core Binding Factor beta Subunit
  • DNA-Binding Proteins / physiology
  • Hematopoiesis
  • Leukemia, Myelomonocytic, Acute / etiology*
  • Mice
  • Oncogene Proteins, Fusion / physiology*
  • Transcription Factor AP-2
  • Transcription Factors / physiology

Substances

  • CBFbeta-MYH11 fusion protein
  • Cbfb protein, mouse
  • Core Binding Factor alpha Subunits
  • Core Binding Factor beta Subunit
  • DNA-Binding Proteins
  • Oncogene Proteins, Fusion
  • Transcription Factor AP-2
  • Transcription Factors
  • core binding factor alpha