Linezolid Acts as a Selective Inhibitor of the JAK2 V617F Mutation - PubMed
5 hours ago
- #Linezolid
- #JAK2 V617F mutation
- #Polycythemia Vera
- Linezolid (LZD) acts as a selective inhibitor of the JAK2 V617F mutation, a driver mutation found in 95% of polycythemia vera (PV) patients.
- In models, LZD suppressed cell proliferation and STAT5 signaling, altered the cell cycle, and increased apoptosis specifically in JAK2 V617F-harboring cells, not in wild-type cells.
- Computational modeling showed LZD interacts specifically with mutant JAK2 V617F protein, not with wild-type JAK2.
- In JAK2 V617F mouse models recapitulating human PV, LZD mitigated disease burden by selectively targeting JAK2 V617F stem cells, normalizing spleen size and blood counts.
- LZD inhibited hematopoietic colony formation from patient-derived cells, preferentially targeting primitive progenitors and decreasing JAK2 V617F+ colonies without affecting wild-type colonies.
- The data support evaluating LZD-like molecules as a potential effective therapy for PV and other myeloproliferative neoplasms.