Menin-dependent megakaryocyte proliferation and fibrosis in myeloproliferative neoplasms.

Menin inhibition reduces megakaryocyte proliferation and fibrosis, showing promise as a therapy for myeloproliferative neoplasms with potent anti-tumor activity.

• Why it matters: Understanding how menin influences megakaryocyte growth is crucial because these cells drive MPN progression and fibrosis, and current treatments have limited efficacy.
• What they did: Researchers used the menin inhibitor revumenib in human cell cultures, mouse models, and primary patient samples, confirming its effects through genetic knockout of MEN1 and MEF2C.
• The result: Menin inhibition decreased megakaryocyte progenitors, suppressed MPN phenotypes, and demonstrated on-target activity, supporting further development of menin-targeted therapies for MPNs.