Document Detail


Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia.
MedLine Citation:
PMID:  21207414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Takayuki Ikezoe; Shinsuke Kojima; Mutsuo Furihata; Jing Yang; Chie Nishioka; Asako Takeuchi; Mayuka Isaka; H Phillip Koeffler; Akihito Yokoyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-08
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  129     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-09-21     Completed Date:  2011-11-04     Revised Date:  2012-02-28    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2512-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
Affiliation:
Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. ikezoet@kochi-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Aminopyridines / pharmacology
Antigens, CD34 / metabolism
Bone Marrow / chemistry
Female
Humans
Janus Kinase 2 / antagonists & inhibitors,  metabolism*
Leukemia, Myeloid, Acute / drug therapy,  metabolism*,  pathology
Male
Middle Aged
Molecular Targeted Therapy
Prognosis
Pyrazoles / pharmacology
Grant Support
ID/Acronym/Agency:
R01 CA026038-30A2/CA/NCI NIH HHS; R01 CA026038-31/CA/NCI NIH HHS; R01 CA026038-32/CA/NCI NIH HHS; R01 CA026038-33/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/5-fluoro-2-(1-(4-fluorophenyl)ethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)nicotinonitrile; 0/Aminopyridines; 0/Antigens, CD34; 0/Pyrazoles; EC 2.7.10.1/Janus Kinase 2

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