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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-03-0861. This Article Full Text (PDF) All Versions of this Article: 2003-03-0861v1 102/10/3786    most recent Alert me when this article is cited Alert me if a correction is posted 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 El Ouriaghli, F. Articles by Barrett, A J Search for Related Content PubMed PubMed Citation Articles by El Ouriaghli, F. Articles by Barrett, A J Social Bookmarking                   What's this? Submitted March 21, 2003 Accepted July 25, 2003 Clonal dominance of chronic myelogenous leukemia is associated with diminished sensitivity to the antiproliferative effects of neutrophil elastase Frank El Ouriaghli, Elaine M Sloand, Lori Mainwaring, Hiroshi Fujiwara, Keyvan Keyvanfar, J J Melenhorst, Katayoun Rezvani, Giuseppe Sconocchia, Scott Solomon, Nancy Hensel, and A J Barrett* Hematology Branch, National Heart Blood and Lung Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: barrettj{at}nih.gov. Clinical observations suggest that in chronic myelogenous leukemia (CML) the Ph+ clone has a growth advantage over normal hematopoiesis. Patients with CML have high levels of neutrophil elastase, which has recently been shown to antagonize the action of G-CSF and other growth factors. We therefore compared the effect of elastase on the growth of normal and CML progenitor cells. In 10 day suspension cultures of normal or CML CD34+ cells supplemented with G-CSF, SCF and GM-CSF, CML cells had diminished sensitivity to the growth inhibitory effect of elastase. When equal numbers of CML and normal CD34+ cells were co-cultured for 10 days, there was no change in the relative proportions of normal and leukemic cells (measured by FISH or Flow). However when elastase was added, CML cells predominated at the end of the culture period (78 vs 22% with 1µg/mL, and 80 vs 20% with 5µg/mL elastase). CML neutrophils substituted effectively for elastase in suppressing proliferation of normal CD34+ cells, but this effect was abrogated by serine protease inhibitors. These results suggest that elastase overproduction by the leukemic clone can change the growth environment by digestion of growth factors thereby giving advantage to Ph+ hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Draminski, A. Rada-Iglesias, S. Enroth, C. Wadelius, J. Koronacki, and J. Komorowski Monte Carlo feature selection for supervised classification Bioinformatics, January 1, 2008; 24(1): 110 - 117. [Abstract] [Full Text] [PDF] S. Tavor, I. Petit, S. Porozov, P. Goichberg, A. Avigdor, S. Sagiv, A. Nagler, E. Naparstek, and T. Lapidot Motility, proliferation, and egress to the circulation of human AML cells are elastase dependent in NOD/SCID chimeric mice Blood, September 15, 2005; 106(6): 2120 - 2127. [Abstract] [Full Text] [PDF] H. Fujiwara, J. J. Melenhorst, F. El Ouriaghli, S. Kajigaya, M. Grube, G. Sconocchia, K. Rezvani, D. A. Price, N. F. Hensel, D. C. Douek, et al. In vitro Induction of Myeloid Leukemia-Specific CD4 and CD8 T Cells by CD40 Ligand - Activated B Cells Gene Modified to Express Primary Granule Proteins Clin. Cancer Res., June 15, 2005; 11(12): 4495 - 4503. [Abstract] [Full Text] [PDF] H. Fujiwara, F. El Ouriaghli, M. Grube, D. A. Price, K. Rezvani, E. Gostick, G. Sconocchia, J. Melenhorst, N. Hensel, D. C. Douek, et al. Identification and in vitro expansion of CD4+ and CD8+ T cells specific for human neutrophil elastase Blood, April 15, 2004; 103(8): 3076 - 3083. [Abstract] [Full Text] [PDF]

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