Targeting binding partners of the CBFβ-SMMHC fusion protein for the treatment of inversion 16 acute myeloid leukemia

Oncotarget. 2016 Oct 4;7(40):66255-66266. doi: 10.18632/oncotarget.11357.

Abstract

Inversion of chromosome 16 (inv(16)) generates the CBFβ-SMMHC fusion protein and is found in nearly all patients with acute myeloid leukemia subtype M4 with Eosinophilia (M4Eo). Expression of CBFβ-SMMHC is causative for leukemia development, but the molecular mechanisms underlying its activity are unclear. Recently, there have been important advances in defining the role of CBFβ-SMMHC and its binding partners, the transcription factor RUNX1 and the histone deacetylase HDAC8. Importantly, initial trials demonstrate that small molecules targeting these binding partners are effective against CBFβ-SMMHC induced leukemia. This review will discuss recent advances in defining the mechanism of CBFβ-SMMHC activity, as well as efforts to develop new therapies for inv(16) AML.

Keywords: AML; CBFβ; CBFβ-SMMHC; RUNX1; inv(16).

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Chromosome Inversion*
  • Chromosomes, Human, Pair 16*
  • Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Histone Deacetylases / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Protein Binding
  • Protein Interaction Maps / drug effects*
  • Repressor Proteins / antagonists & inhibitors*
  • Repressor Proteins / metabolism

Substances

  • Antineoplastic Agents
  • CBFbeta-MYH11 fusion protein
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 protein, human
  • Repressor Proteins
  • HDAC8 protein, human
  • Histone Deacetylases