Author/Authors :
Krivtsov، نويسنده , , Andrei V. and Feng، نويسنده , , Zhaohui and Lemieux، نويسنده , , Madeleine E. and Faber، نويسنده , , Joerg and Vempati، نويسنده , , Sridhar and Sinha، نويسنده , , Amit U. and Xia، نويسنده , , Xiaobo and Jesneck، نويسنده , , Jonathan and Bracken، نويسنده , , Adrian P. and Silverman، نويسنده , , Lewis B. and Kutok، نويسنده , , Jeffery L. and Kung، نويسنده , , Andrew L. and Armstrong، نويسنده , , Scott A.، نويسنده ,
Abstract :
Summary
ated 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 MLL-rearranged 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-AF4-driven gene expression.
