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https://hdl.handle.net/2440/9451
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Type: | Journal article |
Title: | Chronic myelomonocytic leukemia requires granulocyte-macrophage colony-stimulating factor for growth in vitro and in vivo |
Author: | Ramshaw, H. Bardy, P. Lee, M. Lopez, A. |
Citation: | Experimental Hematology, 2002; 30(10):1124-1131 |
Publisher: | Elsevier Science Inc |
Issue Date: | 2002 |
ISSN: | 0301-472X 1873-2399 |
Statement of Responsibility: | Hayley S. Ramshaw, Peter G. Bardy, Melissa A. Lee and Angel F. Lopez |
Abstract: | <h4>Objective</h4>Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease with no effective treatments or cure. Several factors have been implicated in its pathogenesis. In the current study, we studied the dependence of CMML on granulocyte-macrophage colony-stimulating factor (GM-CSF).<h4>Materials and methods</h4>We used in vitro colony assays in methylcellulose where CMML cells were tested in the presence or absence of the specific GM-CSF antagonist E21R. We also developed an in vivo model in which CMML cells were tested for their ability to engraft into immunodeficient mice transgenic for human GM-CSF.<h4>Results</h4>Bone marrow cells from seven of seven patients with CMML formed spontaneous colonies that were sensitive to E21R treatment, with reduction in colony growth by up to 92%. E21R also inhibited colony formation by CMML patient cells stimulated by exogenously added GM-CSF but not interleukin-3. In in vivo experiments we observed engraftment of CMML cells (but not normal cells) in immunodeficient mice transgenic for human GM-CSF. None engrafted in nontransgenic mice. Cell dose escalation showed that the optimal number was 0.5 to 1 x 10(8) peripheral blood mononuclear cells per mouse, which is equivalent to an infusion of 0.2 to 3.6 x 10(6) CD34(+) cells. Time course experiments showed that maximal engraftment occurred 6 weeks after injection.<h4>Conclusions</h4>These results demonstrate that in some CMML patients, GM-CSF produced by either autocrine or paracrine mechanisms is a major growth determinant. The results suggest that therapies directed at blocking this cytokine could control the growth of some CMML patients in vivo. |
Keywords: | Tumor Cells, Cultured Animals Mice, Inbred NOD Mice, Transgenic Humans Mice Mice, SCID Blast Crisis Leukemia, Myelomonocytic, Chronic Granulocyte-Macrophage Colony-Stimulating Factor DNA Primers Transplantation, Heterologous Cell Division Adult Aged Aged, 80 and over Female Male |
Description: | Copyright © 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. |
DOI: | 10.1016/S0301-472X(02)00903-7 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/601451/description#description |
Published version: | http://dx.doi.org/10.1016/s0301-472x(02)00903-7 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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