Preclinical rationale for TGF-β inhibition as a therapeutic target for the treatment of myelofibrosis.

ABSTRACT: To assess the role of abnormal transforming growth factor-beta (TGF-β) signaling in the pathogenesis of primary myelofibrosis (PMF), the effects of the TGF-β receptor-1 kinase inhibitor SB431542 on ex vivo expansion of hematopoietic cells in cultures from patients with JAK2V617⁺-polycythemia vera (PV) or PMF (JAK2V617F⁺, CALRpQ365f⁺, or unknown) and from normal sources (adult blood, AB, or cord blood, CB) were compared. In cultures of normal sources, SB431542 significantly increased by 2.5-fold the number of progenitor cells generated by days 1-2 (CD34⁺) and 6 (colony-forming cells) (CB) and that of precursor cells, mostly immature erythroblasts, by days 14-17 (AB and CB). In cultures of JAK2V617F⁺-PV, SB431542 increased by twofold the

SUBMITTER: Ceglia I 

PROVIDER: S-EPMC5778911 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature