Challenges and Perspectives for Therapeutic Targeting of Myeloproliferative Neoplasms.

ABSTRACT: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders with dysregulated myeloid blood cell production and propensity for transformation to acute myeloid leukemia, thrombosis, and bleeding. Acquired mutations in JAK2, MPL, and CALR converge on hyperactivation of Janus kinase 2 (JAK2) signaling as a central feature of MPN. Accordingly, JAK2 inhibitors have held promise for therapeutic targeting. After the JAK1/2 inhibitor ruxolitinib, similar JAK2 inhibitors as fedratinib are entering clinical use. While patients benefit with reduced splenomegaly and symptoms, disease-modifying effects on MPN clone size and clonal evolution are modest. Importantly, response to ruxolitinib may be lost upon treatment suggesting the MPN clone acquires resistance. Resista

SUBMITTER: Brkic S 

PROVIDER: S-EPMC7773330 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature