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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4646-4655. Prepublished online as a Blood First Edition Paper on February 10, 2009; DOI 10.1182/blood-2008-08-174037. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2008-08-174037v1 113/19/4646    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kennah, E. Articles by Jiang, X. Search for Related Content PubMed PubMed Citation Articles by Kennah, E. Articles by Jiang, X. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells Erin Kennah1,2, Ashley Ringrose1, Liang L. Zhou1, Sharmin Esmailzadeh1,2, Hong Qian3, Ming-wan Su4, Youwen Zhou4, and Xiaoyan Jiang1,2 1 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC; 2 Department of Medical Genetics, University of British Columbia, Vancouver, BC; 3 Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC; and 4 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC AHI-1 is an oncogene often targeted by provirus insertional mutagenesis in murine leukemias and lymphomas. Aberrant expression of human AHI-1 occurs in cutaneous T-cell lymphoma (CTCL) cells and in CD4+CD7– Sezary cells from patients with Sezary syndrome. Stable knockdown of AHI-1 using retroviral-mediated RNA interference in CTCL cells inhibits their transforming activity in vitro and in vivo. To identify genes involved in AHI-1–mediated transformation, microarray analysis was performed to identify differentially expressed genes in AHI-1–suppressed CTCL cells. Fifteen up-regulated and 6 down-regulated genes were identified and confirmed by quantitative reverse transcription-polymerase chain reaction. Seven were further confirmed in a microarray analysis of CD4+CD7– Sezary cells from Sezary syndrome patients. HCK and BIN1 emerged as new candidate cooperative genes, with differential protein expression, which correlates with observed transcript changes. Interestingly, changes in HCK phosphorylation and biologic response to its inhibitor, dasatinib, were observed in AHI-1–suppressed or –overexpressed cells. The tumor suppressor BIN1 physically interacts with MYC in CTCL cells, which also exhibit differential MYC protein expression. In addition, aberrant expression of alternative splicing forms of BIN1 was observed in primary and transformed CTCL cells. These findings indicate that HCK and BIN1 may play critical roles in AHI-1–mediated leukemic transformation of human CTCL cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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