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USP22 is a novel vulnerability regulating MEIS1 protein abundance and gene transcription in KMT2Ar acute leukemia.
Blood · · Journal Article
Bröchtel, Schneider + more
Abstract ↗AI summary
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USP22 regulates MEIS1 protein stability in KMT2Ar B-cell acute lymphoblastic leukemia, and USP22 inhibition triggers MEIS1 polyubiquitination and proteasomal degradation.
- Why it matters: KMT2A-rearranged acute leukemia has poor outcomes and can resist menin inhibitors, so new vulnerabilities are needed to suppress leukemogenic transcription.
- What they did: A genome-wide CRISPR/Cas9 screen in a KMT2Ar B-ALL cell line identified USP22; depletion impaired growth, and ChIP showed USP22 and MEIS1 co-occupy oncogenic target genes.
- The result: Genetic or chemical USP22 inhibition increased MEIS1 polyubiquitination, promoted proteasomal degradation, and downregulated target gene expression, suggesting USP22 as a therapeutic vulnerability in KMT2Ar leukemias.
The findingWhy it mattersWhat they didThe result
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