TCA-controlled histone succinylation identifies IDH3B as a prognostic and therapeutic target in AML.
A newly identified protein in leukemia stem cells offers a potential way to overcome drug resistance in certain blood cancers.
Through integrated proteomics and transcriptomics, this study identified IDH3B—a TCA cycle enzyme—as overexpressed in AML leukemic stem cells and associated with poor prognosis. IDH3B deletion elevated histone succinylation, suppressed MYC transcription at the H3K79 methylation level, and sensitized KMT2A-rearranged AML to Revumenib (menin inhibitor), establishing IDH3B as a candidate target to overcome menin-inhibitor resistance.
What the study was
- Study design
- preclinical
- Category
- AML biology / epigenetics
- Maturity
- Exploratory
- Journal
- Clinical Epigenetics
Why it surfaced
Novel metabolic-epigenetic axis (TCA cycle→IDH3B→histone succinylation→MYC) in AML provides mechanistic rationale for combining IDH3B inhibition with menin inhibitors (Revumenib), a clinically approved drug class. KMT2A-rearranged AML has high unmet need. Demonstrates in vivo preclinical proof-of-concept.
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