| Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia. | |
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MedLine Citation:
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PMID: 21207414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-04-08 |
Journal Detail:
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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:
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Created Date: 2011-09-21 Completed Date: 2011-11-04 Revised Date: 2012-02-28 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 2512-21 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 UICC. |
Affiliation:
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Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. ikezoet@kochi-u.ac.jp |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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