[PDF][PDF] H3K79 methylation profiles define murine and human MLL-AF4 leukemias

AV Krivtsov, Z Feng, ME Lemieux, J Faber, S Vempati… - Cancer cell, 2008 - cell.com
AV Krivtsov, Z Feng, ME Lemieux, J Faber, S Vempati, AU Sinha, X Xia, J Jesneck…
Cancer cell, 2008cell.com
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 MLL-rearranged ALLs could …
Summary
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 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.
cell.com