H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias

Andrei V. Krivtsov, Zhaohui Feng, Madeleine E. Lemieux, Joerg Faber, Sridhar Vempati, Amit U. Sinha, Xiaobo Xia, Jonathan Jesneck, Adrian P. Bracken, Lewis B. Silverman, Jeffery L. Kutok, Andrew L. Kung (+1 others)
2008 Cancer Cell  
We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human MLL-rearranged leukemias. Human
more » ... d ALLs could be distinguished from other ALLs by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4driven gene expression.
doi:10.1016/j.ccr.2008.10.001 pmid:18977325 pmcid:PMC2591932 fatcat:x3ltqr6l4fad7owrzihm3vf22m