# Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms

## TL;DR

This study shows that crizotinib, a cancer drug, can help treat low platelet counts in myelodysplastic neoplasms by promoting megakaryocyte maturation.

## Contribution

The novel finding is that crizotinib promotes megakaryocyte maturation by targeting Aurora kinases, not its usual targets.

## Key findings

- Crizotinib induces megakaryocyte polyploidization and platelet production in MDS models.
- Crizotinib alleviates thrombocytopenia in preclinical MDS models.
- The drug's effect is mediated through Aurora kinases, not ALK/ROS1/c-MET.

## Abstract

Current therapeutic options for myelodysplastic neoplasms (MDS)-associated thrombocytopenia are limited. Megakaryocyte maturation might be an innovative therapeutic strategy because its dysregulation profoundly contributes to MDS pathogenesis. Here, we identified crizotinib, a clinically approved anti-cancer drug for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer, as a potent inducer of megakaryocyte maturation. We demonstrated that crizotinib effectively induced polyploidization to increase the platelet-producing capacity of megakaryocytes derived from an MDS murine model and MDS patients by targeting Aurora kinases rather than its canonical targets, ALK/ROS1/c-MET. Importantly, crizotinib administration substantially ameliorated thrombocytopenia in our preclinical model. Our findings underscore the remarkable potential of crizotinib for drug repurposing and offer a novel therapeutic strategy for MDS patients with thrombocytopenia facing health-related quality of life concerns.