Targeting PP2A-dependent autophagy enhances sensitivity to ruxolitinib in JAK2^V617F myeloproliferative neoplasms.

ABSTRACT: The Janus kinase 2 (JAK2)-driven myeloproliferative neoplasms (MPNs) are chronic malignancies associated with high-risk complications and suboptimal responses to JAK inhibitors such as ruxolitinib. A better understanding of cellular changes induced by ruxolitinib is required to develop new combinatory therapies to improve treatment efficacy. Here, we demonstrate that ruxolitinib induced autophagy in JAK2^V617F cell lines and primary MPN patient cells through the activation of protein phosphatase 2A (PP2A). Inhibition of autophagy or PP2A activity along with ruxolitinib treatment reduced proliferation and increased the death of JAK2^V617F cells. Accordingly, proliferation and clonogenic potential of JAK2^V617F-driven primary MPN patient cells, but not of normal

SUBMITTER: Courdy C 

PROVIDER: S-EPMC10330179 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature