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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4168-4170. Prepublished online as a Blood First Edition Paper on January 16, 2007; DOI 10.1182/blood-2006-09-047399. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-047399v1 109/10/4168    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 Walter, R. B. Articles by Appelbaum, F. R. Search for Related Content PubMed PubMed Citation Articles by Walter, R. B. Articles by Appelbaum, F. R. Related Collections Neoplasia Gene Expression Brief Reports Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Brief Report CD33 expression and P-glycoprotein–mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy Roland B. Walter1,2, Ted A. Gooley1, Vincent H. J. van der Velden3, Michael R. Loken4, Jacques J. M. van Dongen3, David A. Flowers1, Irwin D. Bernstein1,5, and Frederick R. Appelbaum1,6 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Department of Medicine, Division of Hematology, University of Washington, Seattle; 3 Department of Immunology, University Medical Center Rotterdam, Erasmus MC, The Netherlands; 4 HematoLogics, Seattle, WA; 5 Department of Pediatrics, University of Washington, Seattle; 6 Department of Medicine, Division of Medical Oncology, University of Washington, Seattle Gemtuzumab ozogamicin (GO) contains an anti-CD33 antibody to facilitate uptake of a toxic calicheamicin-1 derivative. While recent in vitro data demonstrated a quantitative relationship between CD33 expression and GO cytotoxicity, previous correlative studies failed to identify a significant association between CD33 expression and clinical outcome. Studying patients undergoing GO monotherapy for relapsed acute myeloid leukemia (AML), we now find that AML blasts of responders have a significantly higher mean CD33 level and lower P-glycoprotein (Pgp) activity compared with nonresponders. CD33 expression and Pgp activity are inversely correlated. While both variables are associated with outcome, Pgp remains significantly associated with outcome even after adjusting for CD33, whereas CD33 does not show such an association after adjusting for Pgp. The inverse relationship between CD33 and Pgp suggests a maturation-stage–dependent expression of both proteins, and offers the rationale for using cell differentiation–promoting agents to enhance GO-induced cytotoxicity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Chevallier, J. Delaunay, P. Turlure, A. Pigneux, M. Hunault, R. Garand, T. Guillaume, H. Avet-Loiseau, N. Dmytruk, S. Girault, et al. Long-Term Disease-Free Survival After Gemtuzumab, Intermediate-Dose Cytarabine, and Mitoxantrone in Patients With CD33+ Primary Resistant or Relapsed Acute Myeloid Leukemia J. Clin. Oncol., November 10, 2008; 26(32): 5192 - 5197. [Abstract] [Full Text] [PDF] M. Bornhauser, T. Illmer, U. Oelschlaegel, J. Schetelig, R. Ordemann, M. Schaich, M. Hanel, U. Schuler, C. Thiede, A. Kiani, et al. Gemtuzumab Ozogamicin as Part of Reduced-Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Relapsed Acute Myeloid Leukemia Clin. Cancer Res., September 1, 2008; 14(17): 5585 - 5593. [Abstract] [Full Text] [PDF]

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