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Blood, 15 January 2008, Vol. 111, No. 2, pp. 865-873. Prepublished online as a Blood First Edition Paper on October 24, 2007; DOI 10.1182/blood-2007-05-092486. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-092486v1 111/2/865    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 Gattei, V. Articles by Del Poeta, G. Search for Related Content PubMed PubMed Citation Articles by Gattei, V. Articles by Del Poeta, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 31, 2007 Accepted October 22, 2007 Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia Valter Gattei*, Pietro Bulian, Maria Ilaria Del Principe, Antonella Zucchetto, Luca Maurillo, Francesco Buccisano, Riccardo Bomben, Michele Dal-Bo, Fabrizio Luciano, Francesca M Rossi, Massimo Degan, Sergio Amadori, and Giovanni Del Poeta Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (Pordenone), Italy Chair of Hematology, S. Eugenio Hospital and University of Tor Vergata, Rome, Italy * Corresponding author; email: vgattei{at}cro.it. CD49d/4-integrin is variably expressed in chronic lymphocytic leukemia (CLL). We evaluated its relevance as independent prognosticator for overall survival (OS) and time-to-treatment (TTT) in a series of 303 (232 for TTT) CLL, in comparison with other biological or clinical prognosticators (CD38, ZAP-70, IGHV gene status, cytogenetic abnormalities, soluble CD23, 2-microglobulin, Rai-staging). Flow cytometric detection of CD49d was stable and reproducible, and the chosen cut-off (30% CLL cells) easily discriminated CD49dlow from CD49dhigh cases. CD49d, whose expression was strongly associated with that of CD38 (p=2.2x10-16) and ZAP-70 (p=2.6x10-5), or with IGHV mutations (p=1.1x10-6), was independent prognosticator for OS along with IGHV mutational status (CD49d hazard ratio, HRCD49d=3.52, p=0.02; HRIGHV=6.53, p=0.0004) or, if this parameter was omitted, with ZAP-70 (HRCD49d=3.72, p=0.002; HRZAP-70=3.32, p=0.0091). CD49d was also a prognosticator for TTT (HR=1.74, p=0.007) and refined the impact of all the other factors. Notably, a CD49dhigh phenotype, while not changing the outcome of good prognosis (ZAP-70low, mutated-IGHV) CLL, was necessary to correctly prognosticate the shorter TTT of ZAP-70high (HR=3.12; p=0.023) or unmutated-IGHV (HR=2.95; p=0.002) cases.These findings support the introduction of CD49d detection in routine prognostic assessment of CLL patients, and suggest both pathogenetic and therapeutic implications for CD49d expression in CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Rossi, A. Zucchetto, F. M. Rossi, D. Capello, M. Cerri, C. Deambrogi, S. Cresta, S. Rasi, L. De Paoli, C. L. Bodoni, et al. CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia Haematologica, October 1, 2008; 93(10): 1575 - 1579. [Abstract] [Full Text] [PDF] T. D. Shanafelt, C. Hanson, G. W. Dewald, T. E. Witzig, B. LaPlant, J. Abrahamzon, D. F. Jelinek, and N. E. Kay Karyotype Evolution on Fluorescent In Situ Hybridization Analysis Is Associated With Short Survival in Patients With Chronic Lymphocytic Leukemia and Is Related to CD49d Expression J. Clin. Oncol., May 10, 2008; 26(14): e5 - e6. [Full Text] [PDF]

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