This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-4750v1 69/16/6387    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 Citing Articles Citing Articles via HighWire Google Scholar Articles by Vlad, A. Articles by Ledoux, D. PubMed PubMed Citation Articles by Vlad, A. Articles by Ledoux, D.

Down-regulation of CXCR4 and CD62L in Chronic Lymphocytic Leukemia Cells Is Triggered by B-Cell Receptor Ligation and Associated with Progressive Disease

¹ UMR U978 Institut National de la Santé et de la Recherche Médicale-Université Paris 13, UFR SMBH and ² AP-HP, Service d'hématologie biologique, Hôpital Avicenne, Bobigny, France

Requests for reprints: Dominique Ledoux and Florence Ajchenbaum-Cymbalista, UMR U978 Institut National de la Santé et de la Recherche Médicale-Université Paris 13, UFR SMBH, 74 rue Marcel Cachin, 93000 Bobigny, France. Phone: 33-0-1-48-95-59-28; Fax: 33-0-1-48-95-56-27; E-mail: dominique.ledoux{at}avc.aphp.fr and florence.cymbalista{at}avc.aphp.fr.

Key Words: CLL • B-cell receptor • tumor environment • CXCR4 • CD62L

Progressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in the accumulation of malignant B cells. We investigated on CLL cells from 30 untreated patients the consequence of B-cell receptor (BCR) triggering on the membrane expression of CXCR4 and CD62L, two surface molecules involved in trafficking and exit of B-lymphocytes from lymph nodes. BCR stimulation promoted a strictly simultaneous down-regulation of CXCR4 and CD62L membrane expression to a variable extent. The variable BCR-dependent decrease of the two proteins was strikingly representative of the heterogeneous capacity of the CLL cells to respond to BCR engagement in a given patient. Functionally, cells down-regulating CXCR4 and CD62L in response to BCR engagement displayed a reduction in both migration toward CXCL12 and adhesion to lymphatic endothelial cells. Remarkably, the ability of CLL cells to respond to BCR ligation was correlated with unfavorable prognostic markers and short progression-free survival. In conclusion, BCR signaling promotes decrease of CXCR4 and CD62L membrane expression in progressive cases only. These results are consistent with the hypothesis that BCR-mediated signaling pathways favor accumulation of a proliferative pool within the lymph nodes of progressive CLL cases. [Cancer Res 2009;69(16):6387–95]

This article has been cited by other articles:

				D. Crowther-Swanepoel, M. Qureshi, M. J. S. Dyer, E. Matutes, C. Dearden, D. Catovsky, and R. S. Houlston Genetic variation in CXCR4 and risk of chronic lymphocytic leukemia Blood, November 26, 2009; 114(23): 4843 - 4846. [Abstract] [Full Text] [PDF]