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Blood, 1 August 2008, Vol. 112, No. 3, pp. 782-792. Prepublished online as a Blood First Edition Paper on May 16, 2008; DOI 10.1182/blood-2007-12-127688. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-12-127688v1 112/3/782    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 Guarini, A. Articles by Foa, R. Search for Related Content PubMed PubMed Citation Articles by Guarini, A. Articles by Foa, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 5, 2007 Accepted April 16, 2008 BCR-ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells Anna Guarini, Sabina Chiaretti, Simona Tavolaro, Roberta Maggio, Nadia Peragine, Franca Citarella, Maria Rosaria Ricciardi, Simona Santangelo, Marilisa Marinelli, Maria Stefania De Propris, Monica Messina, Francesca Romana Mauro, Ilaria Del Giudice, and Robert Foa* Division of Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy Division of Genetics, Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy * Corresponding author; email: rfoa{at}bce.uniroma1.it. Chronic lymphocytic leukemia (CLL) patients exhibit a variable clinical course. In order to investigate the association between clinico-biologic features and responsiveness of CLL cells to anti-IgM stimulation, we evaluated gene expression changes and modifications in cell cycle distribution, proliferation and apoptosis of IgVH mutated (M) and unmutated (UM) samples upon BCR cross-linking. Unsupervised analysis highlighted a different response profile to BCR stimulation between UM and M samples. Supervised analysis identified several genes modulated exclusively in the UM cases upon BCR cross-linking. Functional gene groups, including signal transduction, transcription, cell cycle regulation and cytoskeleton organization, were upregulated upon stimulation in UM cases. Cell cycle and proliferation analyses confirmed that IgM cross-linking induced a significant progression into the G1 phase and a moderate increase of proliferative activity exclusively in UM patients. Moreover, we observed only a small reduction in the percentage of subG0/1 cells, without changes in apoptosis, in UM cases; contrariwise, a significant increase of apoptotic levels was observed in stimulated cells from M cases. These results document that a differential genotypic and functional response to BCR ligation between IgVH M and UM cases is operational in CLL, indicating that response to antigenic stimulation plays a pivotal role in disease progression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Herling, K. A. Patel, N. Weit, N. Lilienthal, M. Hallek, M. J. Keating, and D. Jones High TCL1 levels are a marker of B-cell receptor pathway responsiveness and adverse outcome in chronic lymphocytic leukemia Blood, November 19, 2009; 114(21): 4675 - 4686. [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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O'Brien, S. Lerner, K. R. Coombes, E. Schlette, A. Ferrajoli, L. L. Barron, et al. Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens Blood, April 2, 2009; 113(14): 3168 - 3171. [Abstract] [Full Text] [PDF]

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