The RUNX1/RUNX1T1 network: translating insights into therapeutic options

Exp Hematol. 2021 Feb:94:1-10. doi: 10.1016/j.exphem.2020.11.005. Epub 2020 Nov 17.

Abstract

RUNX1/RUNX1T1 is the most common fusion gene found in acute myeloid leukemia. Seminal contributions by many different research groups have revealed a complex regulatory network promoting leukemic self-renewal and propagation. Perturbation of RUNX1/RUNX1T1 levels and its DNA binding affects chromatin accessibility and transcription factor occupation at multiple gene loci associated with changes in gene expression levels. Exploration of this transcriptional program by targeted RNAi screens uncovered a crucial role of RUNX1/RUNX1T1 in cell cycle progression by regulating CCND2. This dependency results in a high vulnerability toward inhibitors of CDK4 and CDK6 and suggests new avenues for therapeutic intervention against acute myeloid leukemia.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Gene Expression Regulation, Leukemic*
  • Gene Regulatory Networks
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Protein Interaction Maps
  • RUNX1 Translocation Partner 1 Protein / genetics*
  • RUNX1 Translocation Partner 1 Protein / metabolism
  • Transcriptional Activation

Substances

  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein