Title of article :
Efficacy of TG101348, a Selective JAK2 Inhibitor, in Treatment of a Murine Model of JAK2V617F-Induced Polycythemia Vera
Author/Authors :
Wernig، نويسنده , , Gerlinde and Kharas، نويسنده , , Michael G. and Okabe، نويسنده , , Rachel and Moore، نويسنده , , Sandra A. and Leeman، نويسنده , , Dena S. and Cullen، نويسنده , , Dana E. and Gozo، نويسنده , , Maricel and McDowell، نويسنده , , Elizabeth P. and Levine، نويسنده , , Ross L. and Doukas، نويسنده , , John and Mak، نويسنده , , Chi Ching and Noronha، نويسنده , , Glenn and Martin، نويسنده , , Michael J. Ko، نويسنده , , Yon D. and Lee، نويسنده , , Benjamin H. and Soll، نويسنده , , Richard M. and Tefferi، نويسنده , , Ayalew and Hood، نويسنده , , John D. and Gilliland، نويسنده , , D. Gary، نويسنده ,
Abstract :
Summary
ort that TG101348, a selective small-molecule inhibitor of JAK2 with an in vitro IC50 of ∼3 nM, shows therapeutic efficacy in a murine model of myeloproliferative disease induced by the JAK2V617F mutation. In treated animals, there was a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis. There were no apparent toxicities and no effect on T cell number. In vivo responses were correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden assessed by quantitative genomic PCR, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction as assessed by flow cytometric measurement of phosphorylated Stat5.
