期刊
CANCER CELL
卷 13, 期 4, 页码 321-330出版社
CELL PRESS
DOI: 10.1016/j.ccr.2008.02.017
关键词
-
资金
- NHLBI NIH HHS [K23HL04409] Funding Source: Medline
Polycythemia Vera (PV) is a myeloproliferative disorder (MPD) that is commonly characterized by mutant JAK2 (JAK2V617F) signaling, erythrocyte overproduction, and a propensity for thrombosis, progression to myelofibrosis, or acute leukemia. In this study, JAK2V617F expression by human hematopoietic progenitors promoted erythroid colony formation and erythroid engraftment in a bioluminescent xenogeneic immunocompromised mouse transplantation model. A selective JAK2 inhibitor, TG1 01348 (300 nM), significantly inhibited JAK2V617F(+) progenitor-derived colony formation as well as engraftment (120 mg/kg) in xenogeneic transplantation studies. TG1 01348 treatment decreased GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F(+) progenitor differentiation, and inhibited STAT5 as well as GATA S310 phosphorylation. Thus, TG1 01348 may be an effective inhibitor of JAK2V617F(+) MPDs in clinical
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