SEARCH:   Advanced

Blood, 1 March 2005, Vol. 105, No. 5, pp. 2115-2123. Prepublished online as a Blood First Edition Paper on October 28, 2004; DOI 10.1182/blood-2003-12-4290. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4290v1 105/5/2115    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Maeda, T. Articles by Bessho, M. Search for Related Content PubMed PubMed Citation Articles by Maeda, T. Articles by Bessho, M. Related Collections Immunobiology Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma that subsequently progressed to AML Tomoya Maeda, Fumiharu Yagasaki, Maho Ishikawa, Naoki Takahashi, and Masami Bessho From the Department of Internal Medicine (Hematology), Saitama Medical School, Saitama, Japan. We previously reported a novel fusion between TEL and FGFR3 in a patient with peripheral T-cell lymphoma with t(4; 12)(p16;p13). Disease in this patient subsequently progressed to acute myelogenous leukemia (AML) with the same translocation. Sequence analysis of TEL-FGFR3 fusion transcripts suggested that these diseases originated from the same multipotent stem cell. To determine the transforming property of TEL-FGFR3, we established transfectants of this chimeric fusion gene and investigated the major signal pathways of TEL-FGFR3–induced transformation using various signal transduction inhibitors including SU5402 (fibroblast growth factor tyrosine kinase [FGFR TK] inhibitor). Our results indicated that (1) the expression of TEL-FGFR3 but not HLH-TEL-FGFR3 resulted in efficient focus formation in NIH/3T3 cells and conferred interleukin 3 independence to Ba/F3 cells by a constitutive tyrosine kinase activity probably through oligomerization by the HLH domain of TEL; (2) although effector proteins including classical mitogen-activated protein kinase (MAPK), p38 MAPK, phosphatidylinositol 3-kinase (PI3-K), mammalian target or rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT-3) and STAT-5 were activated in TEL-FGFR3 transformants, the growth of the transformants was inhibited by SU5402 (concentration that inhibits 50% [IC50] = 5 µM) and the PI3-K inhibitor, LY294002 (IC50 = 10 µM) and wortmannin (IC50 = 5 µM), but not by U0126, SB203580, or rapamycin; and (3) injection of TEL-FGFR3 transformants induced lethal leukemia into syngeneic mice. Taken together, the leukemogenic potential of TEL-FGFR3 may be mediated in part through PI3-K. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Chen, I. R. Williams, B. H. Lee, N. Duclos, B. J. P. Huntly, D. J. Donoghue, and D. G. Gilliland Constitutively activated FGFR3 mutants signal through PLC{gamma}-dependent and -independent pathways for hematopoietic transformation Blood, July 1, 2005; 106(1): 328 - 337. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020