التفاصيل البيبلوغرافية
| العنوان: |
Uncovering the pathogenesis of large granular lymphocytic leukemia-novel STAT3 and STAT5b mutations. |
| المؤلفون: |
Rajala, Hanna L. M., Porkka, Kimmo, Maciejewski, Jaroslaw P., Loughran, Thomas P., Mustjoki, Satu |
| المصدر: |
Annals of Medicine; May2014, Vol. 46 Issue 3, p114-122, 9p |
| مستخلص: |
Large granular lymphocytic (LGL) leukemia is an incurable chronic disease, characterized by clonal expansion of cytotoxic T- or NK-cells in blood and bone marrow. Cytopenias (anemia, neutropenia) and autoimmune disorders such as rheumatoid arthritis are the most common clinical manifestations of LGL leukemia. Recently, somatic activating STAT3 gene mutations were shown to be specific for LGL leukemia with a prevalence of up to 70%. Analogous mutations in the STAT5b gene were seen in a smaller proportion of patients. These gain-of-function mutations are located in the SH2 domain of STAT3 and affect the phosphotyrosine-SH2 interaction required for dimerization of STAT3. The mutations increase the phosphorylation of STAT3 and STAT5b and enhance the transcriptional activity of the mutated proteins. STAT3 and STAT5b mutations can be used as molecular markers for LGL leukemia diagnostics, and they present novel therapeutic targets for STAT3 and STAT5b inhibitors, which currently are in development for treatment of cancer and autoimmune disorders. [ABSTRACT FROM AUTHOR] |
|
Copyright of Annals of Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |