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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 27, 2008 Accepted April 27, 2008 Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia Stephanie Dulucq, Stephane Bouchet, Beatrice Turcq, Eric Lippert, Gabriel Etienne, Josy Reiffers, Mathieu Molimard, Maja Krajinovic, and Francois-Xavier Mahon* Laboratoire Hematopoiese Leucemique et cible therapeutique, Universite Victor Segalen Bordeaux 2, Bordeaux, France Department of Clinical Pharmacology and Toxicology, Universite Victor Segalen Bordeaux 2, Bordeaux, France Department of Hematology, the Institut Bergonie, Bordeaux, France Research Center CHU Sainte-Justine, Department of Pediatrics and Pharmacology, University of Montreal, Cote Ste-Catherine, Montreal, Canada * Corresponding author; email: francois-xavier.mahon{at}umr5540.u-bordeaux2.fr. 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 ABCB1 (MDR1) genotype. We analysed the three most relevant single nucleotide polymorphisms (SNPs) of MDR1 in 90 CML patients treated with imatinib. Among the patients homozygous for allele 1236T, 85% achieved a major molecular response (MMR) versus 47.7% for the other genotypes (p=0.003). For the G2677T/A polymorphism, the presence of G allele was associated with worse response (77.8 % (TT/TA) vs 47.1% (GG/GA/GT) p=0.018). Individuals with 1236TT genotype had higher imatinib concentrations. One of haplotypes (1236C-2677G -3435C) was statistically linked to less frequent MMR (70% vs 44.6%; p=0.021. Hence, we demonstrated the usefulness of these SNPs 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]

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