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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2407-2415. Prepublished online as a Blood First Edition Paper on June 8, 2006; DOI 10.1182/blood-2006-04-020305.
NEOPLASIA Autocrine release of interleukin-9 promotes Jak3-dependent survival of ALK+ anaplastic large-cell lymphoma cellsFrom the Departments of Hematopathology and Lymphoma/Myeloma, University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Laboratory Medicine and Pathology and Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; and Department of Biological Sciences, University of Texas at El Paso, El Paso, TX.
The aberrant fusion protein NPM-ALK plays an important pathogenetic role in ALK+ anaplastic large-cell lymphoma (ALCL). We previously demonstrated that Jak3 potentiates the activity of NPM-ALK. Jak3 activation is restricted to interleukins that recruit the common
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
chain (
and IL-9 in 3 ALK+ ALCL-cell lines and 75% and 83% of primary tumors, respectively. IL-9 was detected in serum-free culture medium harvested from ALK+ ALCL-cell lines, supporting autocrine release of IL-9. Treatment of these cells with an anti–IL-9–neutralizing antibody decreased pJak3 and its kinase activity, along with pStat3 and ALK kinase activity. These effects were associated with decreased cell proliferation and colony formation in soft agar and cell-cycle arrest. Evidence suggests that cell-cycle arrest can be attributed to up-regulation of p21 and down-regulation of Pim-1. Our results illustrate that IL-9/Jak3 signaling plays a significant role in the pathogenesis of ALK+ ALCL and that it represents a potential therapeutic target for treating patients with ALK+ ALCL. 
