This study investigated whether menin inhibition (via revumenib) reduces megakaryocyte proliferation and fibrosis in myeloproliferative neoplasms (MPNs), using human CD34+ cultures, MPN patient specimens, and mouse models — including genetic knockout of MEN1 and its target MEF2C to confirm on-target effects.
Revumenib showed potent anti-tumor activity in MPN models, synergized with ruxolitinib, suppressed megakaryopoiesis in primary MPN patient specimens both in vitro and in vivo, and caused only subtle effects in healthy mice; MEN1 and MEF2C knockout phenocopied drug effects.
Results are largely preclinical (cell cultures and mouse models); clinical MPN patient data are limited to in vitro and in vivo specimen studies without a formal trial. The observed thrombocytopenia signal (15–20%) comes from heavily pre-treated leukemia patients, which may not reflect MPN populations.
Menin inhibition with revumenib is a candidate therapy for MPNs, particularly in combination with ruxolitinib, but clinical trials in MPN patients are needed before practice change. Clinicians using revumenib for leukemia should monitor platelet counts, as megakaryocyte suppression appears to be an on-target drug effect.
Explore related topics
