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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5173-5181. Prepublished online as a Blood First Edition Paper on March 7, 2008; DOI 10.1182/blood-2007-08-108605. This Article Full Text (PDF) All Versions of this Article: blood-2007-08-108605v1 111/10/5173    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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Patten, P. E. Articles by Devereux, S. Search for Related Content PubMed PubMed Citation Articles by Patten, P. E. Articles by Devereux, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 22, 2007 Accepted February 24, 2008 CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment Piers EM Patten*, Andrea GS Buggins, Julie Richards, Andrew Wotherspoon, Jon Salisbury, Ghulam J Mufti, Terry J Hamblin, and Stephen Devereux Department of Haematological and Molecular Medicine, King's College London, The Rayne Institute, London, United Kingdom Department of Histopathology, The Royal Marsden Hospital, London, United Kingdom Department of Histopathology, King's College London, London, United Kingdom * Corresponding author; email: piers.patten{at}kcl.ac.uk. Chronic lymphocytic leukemia is a lymphoproliferative disease with a highly variable outcome. The prognosis of patients with CLL may be predicted using a number of biomarkers including the level of CD38 expression at the leukemic cell surface. This study investigates the hypothesis that CD38 expression by CLL cells reflects interactions with non-malignant cells within pseudofollicles in secondary lymphoid tissue where tumor cell proliferation is believed to occur. We find that CD38 expression is higher in tissues that contain pseudofollicles compared to those that do not. In addition, we show that CD38 expression in CLL is dynamic, changes in response to contact with activated CD4+ T-cells and identifies cells that are primed to proliferate. Finally, we demonstrate close contact between activated CD4+ T-cells and proliferating tumor in primary patient tissue. Proliferating tumor cells in lymph nodes express CD38, which is in turn associated with an increased number of CD31+ vascular endothelial cells. Although the factors resulting in co-localization of tumor, T-cells and endothelium remain unclear, the existence of these cellular clusters may provide an explanation for the association between CD38 expression and adverse outcome in CLL, and suggests novel therapeutic targets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Calissano, R. N. Damle, G. Hayes, E. J. Murphy, M. K. Hellerstein, C. Moreno, C. Sison, M. S. Kaufman, J. E. Kolitz, S. L. Allen, et al. In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia Blood, November 26, 2009; 114(23): 4832 - 4842. [Abstract] [Full Text] [PDF] M. P. Quiroga, K. Balakrishnan, A. V. Kurtova, M. Sivina, M. J. Keating, W. G. Wierda, V. Gandhi, and J. A. 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Hartmann, A. Burkle, W. G. Wierda, M. J. Keating, and A. Rosenwald 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 Blood, March 26, 2009; 113(13): 3050 - 3058. [Abstract] [Full Text] [PDF] V. Grubor, A. Krasnitz, J. E. Troge, J. L. Meth, B. Lakshmi, J. T. Kendall, B. Yamrom, G. Alex, D. Pai, N. Navin, et al. Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA) Blood, February 5, 2009; 113(6): 1294 - 1303. [Abstract] [Full Text] [PDF] T. J. Kipps Chronic Lymphocytic Leukemia: Advances in Assessing Prognosis and Therapy ASCO Educational Book, January 1, 2009; 2009(1): 385 - 393. [Abstract] [Full Text] [PDF] A. D. Hamblin and T. J. Hamblin The immunodeficiency of chronic lymphocytic leukaemia Br. Med. Bull., September 1, 2008; 87(1): 49 - 62. [Abstract] [Full Text] [PDF]

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