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BCR/ABL Studies

BCR/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells

Leukemia volume 19, pages 373–380 (2005)Cite this article

Abstract

The mechanism underlying p210BCR/ABL oncoprotein-mediated transformation in chronic myelogenous leukemia (CML) is not fully understood. We hypothesized that p210BCR/ABL suppresses expression of genes which may explain at least some of the pathogenetic features of CML. A subtractive cDNA library was created between BCR/ABL-enhanced-green-fluorescent-protein (GFP)-transduced umbilical cord blood (UCB) CD34+ cells and GFP-transduced UCB CD34+ cells to identify genes whose expression is downregulated by p210BCR/ABL. At least 100 genes were identified. We have confirmed for eight of these genes that expression was suppressed by quantitative real-time-RT-PCR (Q-RT-PCR) of additional p210BCR/ABL-transduced CD34+ UCB cells as well as primary early chronic phase (CP) bone marrow (BM) CML CD34+ cells. Imatinib mesylate reversed downregulation of some genes, to approximately normal levels. Several of the genes are implicated in cell adhesion and motility, including L-selectin, intercellular adhesion molecule-1 (ICAM-1), and the chemokine receptor, CCR7, consistent with the known defect in adhesion and migration of CML cells. Compared with GFP UCB or normal (NL) BM CD34+ cells, p210 UCB and CML CD34+ cells migrated poorly towards the CCR7 ligands, CCL19 and CCL21, suggesting a possible role for CCR7 in the abnormal migratory behavior of CML CD34+ cells.

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Acknowledgements

This work was supported by Dutch Cancer Society, Grant RO1 HL-49930-10.

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  1. M Jongen-Lavrencic and S Salesse: These authors contributed equally.

Authors and Affiliations

  1. Department of Medicine, University of Minnesota, Stem Cell Institute, Cancer Center, Minneapolis, MN, USA

    M Jongen-Lavrencic, S Salesse & C M Verfaillie

  2. Department of Hematology, Erasmus MC, Rotterdam, The Netherlands

    M Jongen-Lavrencic & R Delwel

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  1. M Jongen-Lavrencic
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Correspondence to C M Verfaillie.

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Jongen-Lavrencic, M., Salesse, S., Delwel, R. et al. BCR/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells. Leukemia 19, 373–380 (2005). https://doi.org/10.1038/sj.leu.2403626

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