Carfilzomib Enhances the Suppressive Effect of Ruxolitinib in Myelofibrosis.

ABSTRACT: As the first FDA-approved tyrosine kinase inhibitor for treatment of patients with myelofibrosis (MF), ruxolitinib improves clinical symptoms but does not lead to eradication of the disease or significant reduction of the mutated allele burden. The resistance of MF clones against the suppressive action of ruxolitinib may be due to intrinsic or extrinsic mechanisms leading to activity of additional pro-survival genes or signalling pathways that function independently of JAK2/STAT5. To identify alternative therapeutic targets, we applied a pooled-shRNA library targeting ~5000 genes to a JAK2^V617F-positive cell line under a variety of conditions, including absence or presence of ruxolitinib and in the presence of a bone marrow microenvironment-like culture medium. We identif

SUBMITTER: Claudiani S 

PROVIDER: S-EPMC8507927 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature