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  2. Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia

Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia

  • Int J Cancer. 2011 Nov 15;129(10):2512-21. doi: 10.1002/ijc.25910.
Takayuki Ikezoe 1 Shinsuke Kojima Mutsuo Furihata Jing Yang Chie Nishioka Asako Takeuchi Mayuka Isaka H Phillip Koeffler Akihito Yokoyama
Affiliations

Affiliation

  • 1 Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. ikezoet@kochi-u.ac.jp
Abstract

Our study determined if Janus kinase 2 (JAK2) was activated in acute myelogenous leukemia (AML; n = 77, excluding acute promyelocytic leukemia) by immunohistochemistry (IHC) using a phosphor-specific antibody against JAK2. p-JAK2 was detectable in all cases, although its levels varied between patient samples (high levels, n = 31; low levels, n = 46). The quantification of levels of p-JAK2 by IHC was well correlated with that assessed by Western blot analyses and fluorescence-activated cell sorting (FACS). Levels of p-JAK2 were directly correlated with high white blood cell count (52.3 × 10(3) /L in patients with high p-JAK2 vs. 28.3 × 10(3) /L in patients with low p-JAK2, p < 0.01) and were inversely correlated with complete remission rates (45% in patients with high p-JAK2 vs. 78% in patients with low p-JAK2, p < 0.003). In addition, multivariate analysis confirmed that high levels of p-JAK2 remained a significant factor for overall survival (hazard ratio = 2.213; 95% confidence interval, 1.212-4.041, p = 0.023). Moreover, we found that AZ960, a novel and specific inhibitor of the JAK2 kinase, potently inhibited the clonogenic growth and induced Apoptosis of freshly isolated AML cells from patients in association with cleavage of Caspase 3 and downregulation of anti-apoptotic Bcl-xL proteins. Taken together, JAK2 may be a promising molecular target for treatment of AML.

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