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A novel role for transcription factor NFE2 in regulating redox responses and chemotherapy resistance in acute myeloid leukemia [RNA-seq]

ABSTRACT: Elevated activity of transcription factor NFE2 is sufficient to cause leukemic transformation in absence of a classical leukemic driver. However, the molecular mechanism promoting NFE2-driven leukemogenesis is not known. Here we report a previously unrecognized role for NFE2 as a key regulator of the oxidative stress response in leukemic cells. Through a comprehensive analysis of NFE2 genomic occupancy and its effect on chromatin accessibility and transcription, we demonstrate that NFE2 regulates glutathione homeostasis as well as the expression of central detoxifying enzymes. NFE2 constituted one of the highest scoring redox-dependencies in MLL-AF9-transformed primary leukemic cells, substantially more significant than the universally recognized redox regulator NRF2. Consequently, NFE2 knockdown sensitized leukemic cells to ferroptosis induction, GSH depletion as well as to cytarabine treatment. Deriving an NFE2 RedOx score, we demonstrate that increased NFE2 activity constitutes an independent predictor of inferior outcome in AML patients at diagnosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE311577 | GEO | 2026/08/17

REPOSITORIES: GEO

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A novel role for transcription factor NFE2 in regulating redox responses and chemotherapy resistance in acute myeloid leukemia [ChIP-seq]

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