Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l

Author:

Deshpande Aniruddha J.123,Chen Liying124,Fazio Maurizio15,Sinha Amit U.123,Bernt Kathrin M.126,Banka Deepti12,Dias Stuart12,Chang Jenny123,Olhava Edward J.7,Daigle Scott R.7,Richon Victoria M.7,Pollock Roy M.7,Armstrong Scott A.1238

Affiliation:

1. Division of Hematology/Oncology, Children's Hospital,

2. Department of Pediatric Oncology and Harvard Medical School, Boston, MA;

3. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY;

4. Department of Molecular and Cellular Biology, Harvard University, Boston, MA;

5. Functional Genomics of Cancer Unit, Scientific Institute S. Raffaele, Milan, Italy;

6. Department of Pediatrics, University of Colorado Anshutz Medical Campus, Aurora, CO;

7. Epizyme Inc, Cambridge, MA; and

8. Harvard Stem Cell Institute, Boston, MA

Abstract

Key Points Our study demonstrates aberrant genome-wide deposition of histone 3 lysine 79 dimethylation on MLL-target genes in MLL-AF6–driven leukemia cells. We provide evidence that leukemia cells bearing the MLL-AF6 fusion are sensitive to genetic and pharmacologic DOT1L inhibition.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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