Inflammatory mediators differentially regulate megakaryopoiesis and thrombopoiesis in myelofibrosis and essential thrombocythemia.

ABSTRACT: Chronic myeloproliferative neoplasms are characterized by clonal myeloid expansion driven by activating mutations in the JAK2 pathway and chronic inflammation. The aim was to investigate the contribution of circulating inflammatory mediators to the abnormalities in the megakaryocytic lineage characteristic of MF and ET. Plasma samples from 30 MF and 28 ET patients were incubated with normal cord-blood CD34 + progenitors and megakaryo/thrombopoiesis was evaluated. MF plasma increased megakaryocyte output, which was attenuated in sequential samples from ruxolitinib-treated patients. JAK1/2, MAPK and NF-kB inhibitors reverted this effect, revealing the concomitant involvement of all three pathways. Elevated levels of circulating IL-1β and IL-6 correlated with megakaryocyte output, which was r

SUBMITTER: Yanuk DB 

PROVIDER: S-EPMC12701004 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature