The adverse impact of ecotropic viral integration site-1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes.
The Intrinsically Disordered Proteins MLLT3 (AF9) and MLLT1 (ENL) - Multimodal Transcriptional Switches With Roles in Normal Hematopoiesis MLL Fusion Leukemia and Kidney Cancer.
Based on the observation that MLL-AF9 helps to preserve the ongoing gene expression program across multiple cellular contexts study proposes that the rapidly proliferating immature myeloid progenitor cell state initiates transformation when this cell state is perpetuated by MLL-AF9 expression fulfilling the functional definition of malignancy.
This system provides for rapid systematic screening of relative risk dose dependence and combinatorial impact of multitudes of dietary and environmental exposures on MLL-AF9 translocations
Results show that MLL-AF9 reduces Id2 and increases E2-2 expression to drive and sustain leukemia stem cell potential in MLL-rearranged acute myeloid leukemia (AML). Low expression of Id2 or of an Id2 gene signature is associated with poor prognosis in not only MLL-rearranged but also t(8;21) AML patients.
Results show that human MLL-AF9 expression in mouse long-term hematopoietic stem cells causes invasive chemoresistant acute myeloid leukemia that expresses genes related to epithelial-mesenchymal transition.
A luciferase reporter gene assay revealed that hsp70 promoter activation is enhanced by the transcriptional co-activator AF9 and splicing mediator SNRPE but suppressed by the coiled-coil domain-containing protein CCDC127.
Studies identified the evolutionarily conserved Af9 YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.
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