PRMT5 inhibition sensitizes B-cell lymphoma cells to ferroptosis
Combining an experimental drug with an existing compound triggers a two-pronged death pathway in aggressive lymphomas that resisted prior treatment.
PRMT5 was found to protect B-cell lymphoma cells from ferroptotic cell death by upregulating SLC7A11 via an AKT-MYC-ATF5 signaling cascade. Combining the clinical-stage PRMT5 inhibitor GSK3326595 with the ferroptosis inducer dimethyl fumarate showed synergistic tumor suppression in a patient-derived xenograft model, identifying a novel combination strategy for relapsed/refractory DLBCL and MCL.
What the study was
- Study design
- Preclinical in vitro + patient-derived xenograft (PDX) model
- Population
- DLBCL and MCL cell lines and patient-derived xenograft (PDX)
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- Leukemia
Why it surfaced
Novel PRMT5-ferroptosis axis in lymphoma with PDX validation; GSK3326595 is a clinical-stage compound, increasing translational relevance of this combination.
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