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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 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 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 Guarini, A. Articles by Foà, R. Search for Related Content PubMed PubMed Citation Articles by Guarini, A. Articles by Foà, R. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells Anna Guarini1, Sabina Chiaretti1, Simona Tavolaro1, Roberta Maggio1, Nadia Peragine1, Franca Citarella2, Maria Rosaria Ricciardi1, Simona Santangelo1, Marilisa Marinelli1, Maria Stefania De Propris1, Monica Messina1, Francesca Romana Mauro1, Ilaria Del Giudice1, and Robert Foà1 Divisions of 1 Hematology, and 2 Genetics, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy Chronic lymphocytic leukemia (CLL) patients exhibit a variable clinical course. To investigate the association between clinicobiologic 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 up-regulated 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. 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] I. Del Giudice, S. Chiaretti, S. Tavolaro, M. S. De Propris, R. Maggio, F. Mancini, N. Peragine, S. Santangelo, M. Marinelli, F. R. Mauro, et al. Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases Blood, July 16, 2009; 114(3): 638 - 646. [Abstract] [Full Text] [PDF] A. Zucchetto, D. Benedetti, C. Tripodo, R. Bomben, M. Dal Bo, D. Marconi, F. Bossi, D. Lorenzon, M. Degan, F. M. Rossi, et al. CD38/CD31, the CCL3 and CCL4 Chemokines, and CD49d/Vascular Cell Adhesion Molecule-1 Are Interchained by Sequential Events Sustaining Chronic Lymphocytic Leukemia Cell Survival Cancer Res., May 1, 2009; 69(9): 4001 - 4009. [Abstract] [Full Text] [PDF] K. I. Lin, C. S. Tam, M. J. Keating, W. G. Wierda, S. 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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