SEARCH:   Advanced

Blood, 1 September 2008, Vol. 112, No. 5, pp. 2024-2027. Prepublished online as a Blood First Edition Paper on June 4, 2008; DOI 10.1182/blood-2008-03-147744. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-147744v1 112/5/2024    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 Dulucq, S. Articles by Mahon, F.-X. Search for Related Content PubMed PubMed Citation Articles by Dulucq, S. Articles by Mahon, F.-X. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia Stéphanie Dulucq1, Stéphane Bouchet24, Béatrice Turcq1, Eric Lippert1, Gabriel Etienne5, Josy Reiffers5, Mathieu Molimard24, Maja Krajinovic6, and François-Xavier Mahon1 1 Laboratoire Hématopoïèse Leucémique et Cible Thérapeutique, Université Victor Ségalen Bordeaux 2, Inserm U876, Bordeaux, France; 2 Department of Clinical Pharmacology and Toxicology, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France; 3 University Victor Ségalen Bordeaux 2, Bordeaux, France; 4 Inserm U657, Bordeaux, France; 5 Department of Hematology, Institut Bergonié, Regional Cancer Center, Bordeaux, France; and 6 Research Center CHU Sainte-Justine, Department of Pediatrics and Pharmacology, University of Montreal, Cote Ste-Catherine, QC Despite the excellent efficacy of imatinib in chronic myeloid leukemia (CML), the response in patients is heterogeneous, which may in part be caused by pharmacogenetic variability. Imatinib has been reported to be a substrate of the P-glycoprotein pump. In the current study, we focused on the ABCB1 (MDR1) genotype. We analyzed the 3 most relevant single nucleotide polymorphisms of MDR1 in 90 CML patients treated with imatinib. Among the patients homozygous for allele 1236T, 85% achieved a major molecular response versus 47.7% for the other genotypes (P = .003). For the 2677G>T/A polymorphism, the presence of G allele was associated with worse response (77.8%, TT/TA; vs 47.1%, GG/GA/GT; P = .018). Patients with 1236TT genotype had higher imatinib concentrations. One of the haplotypes (1236C-2677G-3435C) was statistically linked to less frequent major molecular response (70% vs 44.6%; P = .021). Hence, we demonstrated the usefulness of these single nucleotide polymorphisms in the identification of CML who may or may not respond optimally to imatinib. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Baccarani, G. Rosti, F. Castagnetti, I. Haznedaroglu, K. Porkka, E. Abruzzese, G. Alimena, H. Ehrencrona, H. Hjorth-Hansen, V. Kairisto, et al. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study Blood, May 7, 2009; 113(19): 4497 - 4504. [Abstract] [Full Text] [PDF] F.-X. Mahon, S. Hayette, V. Lagarde, F. Belloc, B. Turcq, F. Nicolini, C. Belanger, P. W. Manley, C. Leroy, G. Etienne, et al. Evidence that Resistance to Nilotinib May Be Due to BCR-ABL, Pgp, or Src Kinase Overexpression Cancer Res., December 1, 2008; 68(23): 9809 - 9816. [Abstract] [Full Text] [PDF] M. W. Deininger Milestones and Monitoring in Patients with CML Treated with Imatinib Hematology, January 1, 2008; 2008(1): 419 - 426. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020