MRNA profiling in primary AML cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE188638 | GEO | 2022/09/07
REPOSITORIES: GEO
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Project description:Transcriptional dysregulation is a prominent feature in leukemia. Here, we systematically surveyed the transcription factor (TF) vulnerabilities in leukemia, and uncovered TF clusters that exhibit context-specific addictions within and between different subtypes of leukemia. We focused on and validated MEF2D as a requirement exclusively in AML with high IRF8 expression. Transcriptomic and chromatin-binding profiling revealed a key TF circuit composed of MEF2D-IRF8 vital for AML maintenance. AML can acquire dependence on this circuit through various mechanisms, including enhancer activation of the circuit via MLL-rearrangement. IRF8 cooperates with PU.1 to control PU.1/MEIS1 co-regulated transcriptional outputs, meanwhile coordinating with MEF2D to directly regulate genes in a non-redundant manner. Collectively, our study nominates a TF circuit in support of the pathogenesis of AML.
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Project description:Transcriptional dysregulation is a prominent feature in leukemia. Here, we systematically surveyed the transcription factor (TF) vulnerabilities in leukemia, and uncovered TF clusters that exhibit context-specific addictions within and between different subtypes of leukemia. We focused on and validated MEF2D as a requirement exclusively in AML with high IRF8 expression. Transcriptomic and chromatin-binding profiling revealed a key TF circuit composed of MEF2D-IRF8 vital for AML maintenance. AML can acquire dependence on this circuit through various mechanisms, including enhancer activation of the circuit via MLL-rearrangement. IRF8 cooperates with PU.1 to control PU.1/MEIS1 co-regulated transcriptional outputs, meanwhile coordinating with MEF2D to directly regulate genes in a non-redundant manner. Collectively, our study nominates a TF circuit in support of the pathogenesis of AML.
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