RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Academic Article uri icon

Overview

abstract

  • The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product.

publication date

  • January 24, 2013

Research

keywords

  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 4
  • Core Binding Factor Alpha 2 Subunit
  • Gene Expression Regulation, Leukemic
  • Myeloid-Lymphoid Leukemia Protein
  • Oncogene Proteins, Fusion
  • Transcriptional Activation
  • Translocation, Genetic

Identity

PubMed Central ID

  • PMC3607232

Scopus Document Identifier

  • 84873133035

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2012.12.016

PubMed ID

  • 23352661

Additional Document Info

volume

  • 3

issue

  • 1