MLL-AF4 Spreading Identifies Binding Sites that Are Distinct from Super-Enhancers and that Govern Sensitivity to DOT1L Inhibition in Leukemia

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• 作者：Jon Kerry¹ ; Laura Godfrey¹ ; Emmanouela Repapi² ; Marta Tapia¹ ; Neil P. Blackledge³ ; Helen Ma⁴ ; Erica Ballabio¹ ; Sorcha O&rsquo ; Byrne⁵ ; Frida Ponthan⁶ ; Olaf Heidenreich⁶ ; Anindita Roy⁵ ; Irene Roberts¹ ; ⁵ ; Marina Konopleva⁴ ; Robert J. Klose³ ; Huimin Geng⁷ ; Thomas A. Milne¹ ; ⁸ ; ^{thomas.milne@imm.ox.ac.uk}
• 关键词：MLL ; MLL-AF4 ; DOT1L ; H3K79me2 ; leukemia ; epigenetic therapy ; drug combination therapy ; epigenetic spreading
• 刊名：Cell Reports
• 出版年：2017
• 出版时间：10 January 2017
• 年：2017
• 卷：18
• 期：2
• 页码：482-495
• 全文大小：4839 K
• 卷排序：18

文摘

MLL-AF4 binding requires an unmethylated CpG (uCpG) island and Menin MLL-AF4 and Menin can spread into the gene body of some targets Spreading targets are highly transcribed and have an aberrant chromatin signature Spreading of MLL-AF4 is a predictor of sensitivity to DOT1L inhibitors