Epigenetic analysis of Ikaros tumor suppressor function in acute lymphoblastic leukemia
Richman, Alyssa
Richman, Alyssa
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Abstract
Deregulation of chromatin structure is a hallmark of hematologic malignancies that may promote tumorigenesis by silencing tumor suppressor genes, upregulating oncogenes, and inducing genomic instability. IKAROS (encoded by the IKZF1 gene) is a transcription factor that orchestrates epigenetic regulation of developmental gene networks during hematopoiesis and is frequently mutated in acute lymphoblastic leukemia (ALL). Its tumor suppressor role in malignant hematopoiesis, however, remains poorly understood. We investigated IKAROS tumor suppressor function in patient-derived cell models of IKZF1-deleted ALL. We show that induction of wild-type IKZF1 results in global changes in cytosine methylation and chromatin accessibility. Our molecular studies identified a large number of genes with deregulated chromatin in the absence of IKZF1 that may be putative drivers of oncogenesis. Thus, this study establishes a human cell model to elucidate how epigenetic deregulation of transcription contributes to the pathogenesis of human B cell leukemias.
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Graduate
Date
2021-01-01