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Expression changes after loss of Dot1l in murine MLL-AF9 leukemia cells

ABSTRACT: MLL-fusions may induce leukemogenic gene expression programs by recruiting the histone H3K79 methyltransferase to MLL-target promoters. We evaluated gene expression changes after cre-mediated loss of Dot1l in leukemia cells obtained from mice injected with MLL-9 transformed lineage negative bone marrow cells. MLL-AF9 murine leukemia cells carrying two conditional Dot1l alleles were retrovirally transduced with Cre or empty control vector, and gene expression changes were monitored on day 3, 5, and 7 after transduction.

ORGANISM(S): Mus musculus

SUBMITTER: Amit Sinha

PROVIDER: E-GEOD-25911 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L.

Bernt Kathrin M KM Bernt Kathrin M KM Zhu Nan N Sinha Amit U AU Vempati Sridhar S Faber Joerg J Krivtsov Andrei V AV Feng Zhaohui Z Punt Natalie N Daigle Amanda A Bullinger Lars L Pollock Roy M RM Richon Victoria M VM Kung Andrew L AL Armstrong Scott A SA

Cancer cell 20110701 1

The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downre ...[more]

PMID: 21741597

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