Related Experiment Video

Updated: Jul 12, 2026

Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells
09:46

Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood-derived CD34+ Cells

Published on: December 27, 2017

Menin-dependent megakaryocyte proliferation and fibrosis in myeloproliferative neoplasms

Jeremy Wen1, Anitria Cotton1, Rashid Mehmood1

  • 1Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Cancer Cell
|July 9, 2026
PubMed

Insights

Menin inhibition reduces megakaryocyte progenitors, a key driver in myeloproliferative neoplasms (MPNs). This finding supports menin inhibitors as a potential therapy for MPNs.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Menin inhibition is an approved therapy for KMT2A-rearranged and NPM1 mutant acute leukemia.
  • A subset of patients receiving menin inhibition experience decreased platelet counts.
  • Megakaryocytes are implicated in the pathogenesis of myeloproliferative neoplasms (MPNs).

Purpose of the Study:

  • To investigate the mechanism of menin inhibition-induced thrombocytopenia.
  • To evaluate the therapeutic potential of menin inhibition in MPNs.
  • To determine if menin is a dependency in proliferative megakaryocytes.

Main Methods:

  • Utilized human CD34+ cell cultures and mouse models to study megakaryopoiesis.
  • Administered the menin inhibitor revumenib to MPN models.
  • Performed genetic knockout of MEN1 and MEF2C.
  • Assessed the effects of revumenib on primary MPN patient specimens in vitro and in vivo.

Main Results:

  • Menin inhibition reduced megakaryocyte progenitor numbers in vitro and in vivo.
  • The menin inhibitor revumenib demonstrated potent anti-tumor activity in MPN models.
  • Revumenib synergized with ruxolitinib and showed minimal effects on healthy mice.
  • Genetic inactivation of MEN1 and MEF2C mimicked the effects of revumenib, confirming on-target activity.

Conclusions:

  • Menin is essential for the proliferation of megakaryocytes.
  • Menin inhibition effectively suppresses MPN phenotypes.
  • Menin inhibition warrants further investigation as a potential therapeutic strategy for MPNs.
Keywords:
megakaryocytemeninmyeloproliferative neoplasmsrevumenib

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