CD82 regulates STAT5/IL‐10 and supports survival of acute myelogenous leukemia cells. Issue 1 (27th July 2013)

• Record Type: Journal Article
• Authors: Nishioka, Chie; Ikezoe, Takayuki; Yang, Jing; Nobumoto, Atsuya; Kataoka, Sayo; Tsuda, Masayuki; Udaka, Keiko; Yokoyama, Akihito
• Is Part Of: International journal of cancer. Volume 134:Issue 1(2014:Jan. 01)
• Page Start: 55
• Page End: 64
• Publication Date: 2013-07-27
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28348
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We recently reported that adhesion molecule CD82 is aberrantly expressed in CD34<sup>+</sup>/CD38<sup>−</sup> leukemia stem cells (LSCs). Here, we report the results of a functional analysis of CD82 in CD34<sup>+</sup>/CD38<sup>−</sup> acute myelogenous leukemia (AML) cells. Short hairpin (sh)RNA‐mediated downregulation of CD82 resulted in a decrease in the level of IL‐10. In contrast, forced expression of CD82 in CD34<sup>+</sup>/CD38<sup>+</sup> AML cells by transduction with CD82‐expressing lentiviral particles resulted in an increase in the levels of IL‐10. Notably, exposure of CD34<sup>+</sup>/CD38<sup>−</sup> AML cells to IL‐10 stimulated clonogenic growth of these cells. Moreover, downregulation of CD82 by a shRNA dephosphorylated STAT5 in CD34<sup>+</sup>/CD38<sup>−</sup> AML cells. On the other hand, forced expression of CD82 resulted in increase in the levels of p‐STAT5 in CD34<sup>+</sup>/CD38<sup>+</sup> AML cells. Chromatin immunoprecipitation (ChIP) assay results indicated that STAT5A binds to the promoter region of the <italic>IL‐10</italic> gene, while reporter gene assay results indicated stimulation of IL‐10 expression at the transcriptional level. These results suggest that CD82 positively regulates the STAT5/IL‐10 signaling pathway. Moreover, shRNA‐mediated downregulation of CD82 expression in CD34<sup>+</sup>/CD38<sup>‐</sup> AML cells dephosphorylated STAT5 in immunodeficient mice. Taken together, our data suggest that the CD82/STAT5/IL‐10 signaling pathway is involved in the survival of CD34<sup>+</sup>/CD38<sup>−</sup> AML cells and may thus be a promising therapeutic target for eradication of AML LSCs.</p> </abstract>