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Blood, 26 March 2009, Vol. 113, No. 13, pp. 3050-3058. Prepublished online as a Blood First Edition Paper on December 12, 2008; DOI 10.1182/blood-2008-07-170415. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2008-07-170415v1 113/13/3050    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 Burger, J. A. Articles by Rosenwald, A. Search for Related Content PubMed PubMed Citation Articles by Burger, J. A. Articles by Rosenwald, A. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation Jan A. Burger1, Maite P. Quiroga1,*, Elena Hartmann2,*, Andrea Bürkle3, William G. Wierda1, Michael J. Keating1, and Andreas Rosenwald2 1 Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston; 2 Institute of Pathology, University of Würzburg, Würzburg, Germany; and 3 Department of Medicine, Division of Hematology/Oncology, Freiburg University Hospital, Freiburg, Germany In lymphatic tissues, chronic lymphocytic leukemia (CLL) cells are interspersed with CD68+ nurselike cells (NLCs), T cells, and other stromal cells that constitute the leukemia microenvironment. However, the mechanism regulating colocalization of CLL and these accessory cells are largely unknown. To dissect the molecular cross talk between CLL and NLCs, we profiled the gene expression of CD19-purified CLL cells before and after coculture with NLCs. NLC coculture induced high-level expression of B-cell maturation antigen and 2 chemoattractants (CCL3, CCL4) by CLL cells. CCL3/CCL4 induction in NLC cocultures correlated with ZAP-70 expression by CLL cells. High CCL3/CCL4 protein levels were found in CLL cocultures with NLCs, and CCL3/CCL4 induction was abrogated by R406, a Syk inhibitor, suggesting that NLCs induce these chemokines via B-cell receptor (BCR) activation. BCR triggering also caused robust CCL3/CCL4 protein secretion by CLL cells. High CCL3 and CCL4 plasma levels in CLL patients suggest that this pathway plays a role in vivo. These studies reveal a novel mechanism of cross talk between CLL cells and their microenvironment, namely, the secretion of 2 T-cell chemokines in response to NLC coculture and BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells and thereby actively create a supportive microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF] J. A. Burger and V. Gandhi The lymphatic tissue microenvironments in chronic lymphocytic leukemia: in vitro models and the significance of CD40-CD154 interactions Blood, September 17, 2009; 114(12): 2560 - 2561. [Full Text] [PDF] M. P. Quiroga, K. Balakrishnan, A. V. Kurtova, M. Sivina, M. J. Keating, W. G. Wierda, V. Gandhi, and J. A. Burger B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406 Blood, July 30, 2009; 114(5): 1029 - 1037. [Abstract] [Full Text] [PDF]

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