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Blood, 15 November 2003, Vol. 102, No. 10, pp. 3786-3792. Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-03-0861. This Article Full Text 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 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 Ouriaghli, F. E. Articles by Barrett, A. J. Search for Related Content PubMed PubMed Citation Articles by Ouriaghli, F. E. Articles by Barrett, A. J. Related Collections Hematopoiesis and Stem Cells Neoplasia Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Clonal dominance of chronic myelogenous leukemia is associated with diminished sensitivity to the antiproliferative effects of neutrophil elastase Frank El Ouriaghli, Elaine Sloand, Lori Mainwaring, Hiroshi Fujiwara, Keyvan Keyvanfar, J. Joseph Melenhorst, Katayoun Rezvani, Giuseppe Sconocchia, Scott Solomon, Nancy Hensel, and A. John Barrett From the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Clinical observations suggest that in chronic myelogenous leukemia (CML), the Philadelphia chromosome (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 granulocyte-colony-stimulating factor (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, stem cell factor (SCF), and granulocyte macrophage-colony-stimulating factor (GM-CSF), CML cells had diminished sensitivity to the growth inhibitory effect of elastase. When equal numbers of CML and normal CD34+ cells were cocultured for 10 days, there was no change in the relative proportions of normal and leukemic cells (measured by fluorescence in situ hybridization [FISH] or flow cytometry). However, when elastase was added, CML cells predominated at the end of the culture period (78% vs 22% with 1 µg/mL and 80% vs 20% with 5 µg/mL elastase). CML neutrophils substituted effectively for elastase in suppressing the 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 digesting growth factors, thereby giving advantage to Ph+ hematopoiesis. (Blood. 2003; 102:3786-3792) 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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