AML1-FOG2 fusion protein in myelodysplasia

Edward M. Chan, Elisha M. Comer, Frank C. Brown, Kathleen E. Richkind, Melissa L. Holmes, Beng H. Chong, Roger Shiffman, Dong Er Zhang, Marilyn L. Slovak, Cheryl L. Willman, Constance T. Noguchi, Yanjun Li, Devan J. Heiber, Lori Kwan, Rebecca J. Chan, Gail H. Vance, Heather C. Ramsey, Robert A. Hromas

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 GATA developmental programs in the pathogenesis of myelodysplasia.

Original languageEnglish (US)
Pages (from-to)4523-4526
Number of pages4
JournalBlood
Volume105
Issue number11
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Chan, E. M., Comer, E. M., Brown, F. C., Richkind, K. E., Holmes, M. L., Chong, B. H., Shiffman, R., Zhang, D. E., Slovak, M. L., Willman, C. L., Noguchi, C. T., Li, Y., Heiber, D. J., Kwan, L., Chan, R. J., Vance, G. H., Ramsey, H. C., & Hromas, R. A. (2005). AML1-FOG2 fusion protein in myelodysplasia. Blood, 105(11), 4523-4526. https://doi.org/10.1182/blood-2004-07-2762