2. Academic Validation
  3. TAF1 plays a critical role in AML1-ETO driven leukemogenesis

TAF1 plays a critical role in AML1-ETO driven leukemogenesis

  • Nat Commun. 2019 Oct 29;10(1):4925. doi: 10.1038/s41467-019-12735-z.
Ye Xu 1 2,  Na Man 1 3,  Daniel Karl 1 3,  Concepcion Martinez 1 3,  Fan Liu 1 3,  Jun Sun 1 3,  Camilo Jose Martinez 1 3,  Gloria Mas Martin 1 3,  Felipe Beckedorff 1 4,  Fan Lai 1 4,  Jingyin Yue 1 4,  Alejandro Roisman 1 4,  Sarah Greenblatt 1 3,  Stephanie Duffort 2,  Lan Wang 1 3 5,  Xiaojian Sun 1 3 6,  Maria Figueroa 1 4,  Ramin Shiekhattar 1 4,  Stephen Nimer 7 8 9
Affiliations

Affiliations

  • 1 Sylvester Comprehensive Cancer Center, University of Miami, 1120 NW 14th St, Miami, FL, 33136, USA.
  • 2 Department of Medicine, Miller School of Medicine, University of Miami, 1120 NW 14th St, Miami, FL, 33136, USA.
  • 3 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, 1501 NW 10th Ave, Miami, FL, 33136, USA.
  • 4 Department of Human Genetics, Miller School of Medicine, University of Miami, 1120 NW 14th St, Miami, FL, 33136, USA.
  • 5 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 7 Sylvester Comprehensive Cancer Center, University of Miami, 1120 NW 14th St, Miami, FL, 33136, USA. [email protected].
  • 8 Department of Medicine, Miller School of Medicine, University of Miami, 1120 NW 14th St, Miami, FL, 33136, USA. [email protected].
  • 9 Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, 1501 NW 10th Ave, Miami, FL, 33136, USA. [email protected].
PMID: 31664040 DOI: 10.1038/s41467-019-12735-z
Abstract

AML1-ETO (AE) is a fusion transcription factor, generated by the t(8;21) translocation, that functions as a leukemia promoting oncogene. Here, we demonstrate that TATA-Box Binding Protein Associated Factor 1 (TAF1) associates with K43 acetylated AE and this association plays a pivotal role in the proliferation of AE-expressing acute myeloid leukemia (AML) cells. ChIP-sequencing indicates significant overlap of the TAF1 and AE binding sites. Knockdown of TAF1 alters the association of AE with chromatin, affecting of the expression of genes that are activated or repressed by AE. Furthermore, TAF1 is required for leukemic cell self-renewal and its reduction promotes the differentiation and Apoptosis of AE+ AML cells, thereby impairing AE driven leukemogenesis. Together, our findings reveal a role of TAF1 in leukemogenesis and identify TAF1 as a potential therapeutic target for AE-expressing leukemia.

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