Dysregulation of BCL-2 family proteins by leukemia fusion genes

J Biol Chem. 2017 Sep 1;292(35):14325-14333. doi: 10.1074/jbc.R117.799056. Epub 2017 Jul 17.

Abstract

The genomic lesions that characterize acute lymphoblastic leukemia in childhood include recurrent translocations that result in the expression of fusion proteins that typically involve genes encoding tyrosine kinases, cytokine receptors, and transcription factors. These genetic rearrangements confer phenotypic hallmarks of malignant transformation, including unrestricted proliferation and a relative resistance to apoptosis. In this Minireview, we discuss the molecular mechanisms that link these fusions to the control of cell death. We examine how these fusion genes dysregulate the BCL-2 family of proteins, preventing activation of the apoptotic effectors, BAX and BAK, and promoting cell survival.

Keywords: B-cell lymphoma 2 (Bcl-2) family; apoptosis; fusion protein; leukemia; tyrosine-protein kinase (tyrosine kinase).

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Biological*
  • Oncogene Fusion*
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Proto-Oncogene Proteins c-bcl-2 / agonists*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Translocation, Genetic

Substances

  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-bcl-2