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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-06-1822. This Article Full Text (PDF) All Versions of this Article: 2002-06-1822v1 101/3/1087    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 Lanham, S. Articles by Packham, G. Search for Related Content PubMed PubMed Citation Articles by Lanham, S. Articles by Packham, G. Social Bookmarking                   What's this? Submitted June 19, 2002 Accepted August 27, 2002 Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia Stuart Lanham, Terry Hamblin, David Oscier, Rachel Ibbotson, Freda K Stevenson*, and Graham Packham Molecular Immunology Group, Tenovus Research Laboratory, Southampton University Hospitals Trust, Southampton, Hampshire, United Kingdom; Cancer Research UK Oncology Unit, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, Hampshire, United Kingdom Department of Haematology, Royal Bournemouth Hospital, Bournemouth, Dorset, United Kingdom Molecular Immunology Group, Tenovus Research Laboratory, Southampton University Hospitals Trust, Southampton, Hampshire, United Kingdom Cancer Research UK Oncology Unit, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, Hampshire, United Kingdom * Corresponding author; email: fs{at}soton.ac.uk. The mutational status of tumor immunoglobulin VH genes is providing a powerful prognostic marker for chronic lymphocytic leukemia (CLL), with patients having tumors expressing unmutated VH genes being in a less favorable subset. However, the biological differences correlating with VH gene status which could determine the clinical course of the disease are unknown. Here we show that differing responses to IgM ligation are closely associated with VH gene status. Specifically, 80% of cases with unmutated VH genes showed increased global tyrosine phosphorylation following IgM ligation, whereas only 20% of samples with mutated VH genes responded (p=0.0002). There was also an association between response to IgM ligation and expression of CD38 (p=0.015). The Syk kinase, critical for transducing BCR-derived signals, was constitutively present in all CLL samples, and there was a perfect association between global phosphorylation and induction of phosphorylation/activation of Syk. Non-responsiveness to anti-IgM could be circumvented by ligation of IgD (10/15 samples tested) or the BCR-associated molecule CD79 (12/15 samples tested). These results suggest that multiple mechanisms underlie non-responsiveness to anti-IgM in CLL and that retained responsiveness to anti-IgM contributes to the poor prognosis associated with the unmutated subset of CLL. The prognostic power of the in vitro response to IgM ligation remains to be determined in a large series, but the simple technology involved may present an alternative/additional test for predicting clinical course. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. McElligott, E. N. Maginn, L. M. Greene, S. McGuckin, A. Hayat, P. V. Browne, S. Butini, G. Campiani, M. A. Catherwood, E. Vandenberghe, et al. 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