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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
Statement of
Hayley S. Ramshaw, Peter G. Bardy, Melissa A. Lee and Angel F. Lopez
Abstract: OBJECTIVE: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). MATERIALS AND METHODS: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. RESULTS: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. CONCLUSIONS: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
Mice, Inbred NOD
Mice, Transgenic
Mice, SCID
Blast Crisis
Leukemia, Myelomonocytic, Chronic
Granulocyte-Macrophage Colony-Stimulating Factor
DNA Primers
Transplantation, Heterologous
Cell Division
Aged, 80 and over
Description: Copyright © 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.
DOI: 10.1016/S0301-472X(02)00903-7
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