Runx1/AML1 in normal and abnormal hematopoiesis

Int J Hematol. 2005 Jul;82(1):1-8. doi: 10.1532/IJH97.05075.


Runx1/AML1 (also known as CBFA2 and PEBP23B) is a Runt family transcription factor critical for normal hematopoiesis. Runx1 forms a heterodimer with CBF3 and binds to the consensus PEBP2 sequence through the Runt domain. Runx1 enhances gene transcription by interacting with transcriptional coactivators such as p300 and CREB-binding protein. However, Runx1 can also suppress gene transcription by interacting with transcriptional corepressors, including mSin3A, TLE (mammalian homolog of Groucho), and histone deacetylases. Runx1 not only is critical for definitive hematopoiesis in the fetus but also is required for normal megakaryocytic maturation and T-lymphocyte and B-lymphocyte development in adult mice. Runx1 has been identified in leukemia-associated chromosomal translocations, including t(8;21) (Runx1-ETO/MTG8), t(16;21) (Runx1-MTG16), t(3;21) (Runx1-Evi1), t(12;21) (TEL-Runx1), and t(X;21) (Runx1-Fog2). The molecular mechanism of leukemogenesis by these fusion proteins is discussed. Various mutant mice expressing these fusion proteins have been created. However, expression of the fusion protein is not sufficient by itself to cause leukemia and likely requires additional events for leukemogenesis. Point mutations in a Runx1 allele cause haploinsufficiency and a biallelic null for Runx1, which are associated with familial platelet disorder with a propensity for acute myeloid leukemia (FPD/AML) and AML-M0, respectively. Thus, the correct protein structure and the precise dosage of Runx1 are essential for the maintenance of normal hematopoiesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Core Binding Factor Alpha 2 Subunit / physiology*
  • Fetal Development
  • Hematopoiesis / genetics*
  • Hematopoiesis / physiology*
  • Humans
  • Leukemia / genetics*
  • Leukemia / physiopathology*
  • Mice
  • Point Mutation
  • Transcription, Genetic / physiology
  • Translocation, Genetic


  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human