Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy.

ABSTRACT: Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that metal response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2-deficient CD34⁺CD38^- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell-cycle regulation and apoptosis

SUBMITTER: Maganti HB 

PROVIDER: S-EPMC7200079 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature