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This Article Full Text Full Text (PDF) 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 Kitada, S. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Kitada, S. Articles by Reed, J. C. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Expression of Apoptosis-Regulating Proteins in Chronic Lymphocytic Leukemia: Correlations With In Vitro and In Vivo Chemoresponses Shinichi Kitada, Janet Andersen, Sophie Akar, Juan M. Zapata, Shinichi Takayama, Stanislaw Krajewski, Hong-Gang Wang, Xin Zhang, Florencia Bullrich, Carlo M. Croce, Kanti Rai, John Hines, and John C. Reed From the Burnham Institute, Cancer Research Center, La Jolla, CA; Eastern Cooperative Oncology Group, Brookline, MA; The Sidney Kimmel Cancer Center/Thomas Jefferson University, School of Medicine, Philadelphia, PA; The Long Island Jewish Medical Center; and the MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH. B-cell chronic lymphocytic leukemia (B-CLL) represents a neoplastic disorder caused primarily by defective programmed cell death (PCD), as opposed to increased cell proliferation. Defects in the PCD pathway also contribute to chemoresistance. The expression of several apoptosis-regulating proteins, including the Bcl-2 family proteins Bcl-2, Bcl-XL, Mcl-1, Bax, Bak, and BAD; the Bcl-2-binding protein BAG-1; and the cell death protease Caspase-3 (CPP32), was evaluated by immunoblotting using 58 peripheral blood B-CLL specimens from previously untreated patients. Expression of Bcl-2, Mcl-1, BAG-1, Bax, Bak, and Caspase-3 was commonly found in circulating B-CLL cells, whereas the Bcl-XL and BAD proteins were not present. Higher levels of the anti-apoptotic protein Mcl-1 were strongly correlated with failure to achieve complete remission (CR) after single-agent therapy (fludarabine or chlorambucil) (P = .001), but the presence of only seven CRs among the 42 patients for whom follow-up data were available necessitates cautious interpretation of these observations. Higher levels of the anti-apoptotic protein BAG-1 were also marginally associated with failure to achieve CR (P = .04). Apoptosis-regulating proteins were not associated with patient age, sex, Rai stage, platelet count, hemoglobin (Hb) concentration, or lymph node involvement, although higher levels of Bcl-2 and a high Bcl-2:Bax ratio were correlated with high numbers (>105/µL) of white blood cells (WBC) (P = .01; .007) and higher levels of Bak were weakly associated with loss of allelic heterozygosity at 13q14 (P = .04). On the basis of measurements of apoptosis induction by fludarabine using cultured B-CLL specimens, in vitro chemosensitivity data failed to correlate with in vivo clinical response rates (n = 42) and expression of the various apoptosis-regulating proteins. Although larger prospective studies are required before firm conclusions can be reached, these studies show the expression in B-CLLs of multiple apoptosis-regulating proteins and suggest that the relative levels of some of these, such as Mcl-1, may provide information about in vivo responses to chemotherapy. In vitro chemosensitivity data, however, do not appear to be particularly useful in predicting responses in B-CLL. Blood, Vol. 91 No. 9 (May 1), 1998: pp. 3379-3389 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Chen, W. G. Wierda, S. Chubb, R. E. Hawtin, J. A. Fox, M. J. Keating, V. Gandhi, and W. Plunkett Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia Blood, May 7, 2009; 113(19): 4637 - 4645. [Abstract] [Full Text] [PDF] F. T. Awan, N. E. Kay, M. E. Davis, W. Wu, S. M. Geyer, N. Leung, D. F. Jelinek, R. C. Tschumper, C. R. Secreto, T. S. Lin, et al. Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab Blood, January 15, 2009; 113(3): 535 - 537. [Abstract] [Full Text] [PDF] S. M. O'Brien, D. F. 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