Genome-wide analysis of H3K79 methylation in CD34+ CD19+ cells from normal marrow, MLL-rearranged or MLL-germline ALL. Homo sapiens

We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison Overall design: DNA immunoprecipitated with anti-dimethyl-H3K79 antibodies from normal CD34+CD19+ cells, leukemic bone marrow from MLL-rearranged ALL or MLL-germline ALL was hybridized to Affymetrix promoter tiling microarrays.

本研究构建了一款条件性表达生理水平Mll-AF4融合癌基因（Mll-AF4 fusion oncogene）的小鼠模型，该模型可诱发急性淋巴细胞白血病（ALL）或急性髓系白血病（AML）的发生。染色质免疫沉淀芯片（ChIP-chip）分析结果显示，在鼠源ALL以及人类MLL重排白血病中，组蛋白H3赖氨酸79二甲基化（H3K79）水平显著升高，且该修饰水平与Mll-AF4相关的基因表达谱存在显著相关性。此外，人类MLL重排型ALL可通过其全基因组H3K79甲基化谱与其他类型ALL进行区分。
关键词：细胞类型比较
整体实验设计：采用抗二甲基化H3K79抗体，对正常CD34+CD19+细胞、MLL重排型ALL或MLL胚系未重排ALL的白血病骨髓样本进行DNA免疫沉淀，随后将所得免疫沉淀DNA与Affymetrix启动子平铺微阵列进行杂交。