AML1-FOG2 fusion protein in myelodysplasia

Blood. 2005 Jun 1;105(11):4523-6. doi: 10.1182/blood-2004-07-2762. Epub 2005 Feb 10.


Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ZFPM2. The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATAdevelopmental programs in the pathogenesis of myelodysplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases
  • CCAAT-Binding Factor / genetics
  • Chromosomes, Human, Pair 21
  • Chromosomes, Human, X
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Humans
  • Myelodysplastic Syndromes / etiology
  • Myelodysplastic Syndromes / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Repressor Proteins
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Translocation, Genetic


  • AML1-FOG2 fusion protein, human
  • CCAAT-Binding Factor
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Oncogene Proteins, Fusion
  • Phosphoproteins
  • Repressor Proteins
  • Transcription Factors
  • Alcohol Oxidoreductases
  • C-terminal binding protein