JAK2V617F-dependent down regulation of SHP-1 expression participates in the selection of myeloproliferative neoplasm cells in the presence of TGF-β.

ABSTRACT: Myeloproliferative neoplasms (MPNs) are characterized by an increased production of blood cells due to the acquisition of mutations such as JAK2^V617F. TGF-β, whose secretion is increased in MPN patients, is known to negatively regulate haematopoietic stem cell (HSC) proliferation. Using an isogenic JAK2^V617F or JAK2 wild-type UT-7 cell line we observed that JAK2^V617F cells resist to TGF-β antiproliferative activity. Although TGF-β receptors and SMAD2/3 expressions are similar in both cell types, TGF-β-induced phosphorylation of SMAD2/3 is reduced in UT-7 JAK2^V617F cells compared with JAK2 WT cells. We confirmed that JAK2^V617F mutated cells are resistant to the antiproliferative effect of TGF-β in a competitive assay as we observed a po

SUBMITTER: Aoun C 

PROVIDER: S-EPMC11492149 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature