真性红细胞增多症
祖细胞
造血
骨髓纤维化
癌症研究
状态5
移植
生物
干细胞
Janus激酶2
免疫学
细胞生物学
磷酸化
医学
内科学
骨髓
作者
Ifat Geron,Annelie Abrahamsson,Charlene F. Barroga,Edward Kavalerchik,Jason Gotlib,John Hood,Jeffrey A. Durocher,Chi Ching Mak,Glenn Noronha,Richard Söll,Ayalew Tefferi,K Kaushansky,Catriona Jamieson
出处
期刊:Cancer Cell
[Elsevier]
日期:2008-04-01
卷期号:13 (4): 321-330
被引量:128
标识
DOI:10.1016/j.ccr.2008.02.017
摘要
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, TG101348 (300 nM), significantly inhibited JAK2V617F+ progenitor-derived colony formation as well as engraftment (120 mg/kg) in xenogeneic transplantation studies. TG101348 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, TG101348 may be an effective inhibitor of JAK2V617F+ MPDs in clinical trials.
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