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Expression of p‐JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia
Author(s) -
Ikezoe Takayuki,
Kojima Shinsuke,
Furihata Mutsuo,
Yang Jing,
Nishioka Chie,
Takeuchi Asako,
Isaka Mayuka,
Koeffler H. Phillip,
Yokoyama Akihito
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25910
Subject(s) - janus kinase 2 , acute promyelocytic leukemia , medicine , leukemia , immunohistochemistry , clonogenic assay , hazard ratio , myeloid leukemia , apoptosis , cancer research , confidence interval , biology , cell culture , retinoic acid , receptor , biochemistry , genetics
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.