GSE103947 Fusion partner directed chromatin occupancy drives the transcriptome heterogeneity of MLL-fusion acute lymphoblastic leukemia

Contributors : Shan Lin ; Anetta Ptasinska ; Salam A Assi ; Constanze Bonifer ; James C MulloySeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensFusion of the N-terminus of the mixed-lineage-leukemia (MLL) gene with various partner genes drives acute lymphoblastic leukemia (ALL). Despite the fusion proteins sharing some common attributes, transcriptome heterogeneity of MLL-fusion ALL is observed and the underlying mechanism and biological consequences are unknown. We compared the genome-wide occupancy of MLL-Af4 and MLL-AF9 in human ALL cells expressing FLAG-tagged fusion proteins. Although both oncoproteins retain the same MLL N-terminal domains that mediate chromatin binding, the two fusion proteins displayed largely non-overlapping binding profiles, with MLL-AF9 showing preferential binding at repetitive elements. The binding specificity of each fusion protein was associated with differential global gene activation distinguishing the two ALLs. A subset of prednisolone response genes were among the differentially regulated targets, and the resistance related genes were specifically upregulated in MLL-Af4/AF4 cells. These studies provide evidence that distinct chromatin occupancy of different MLL-fusion proteins is one driving force for transcriptome heterogeneity of MLL-fusion ALL, which could potentially result in the disparate therapeutic outcome of the disease.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research