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Blood, 13 August 2009, Vol. 114, No. 7, pp. 1383-1386. Prepublished online as a Blood First Edition Paper on June 10, 2009; DOI 10.1182/blood-2008-11-191098. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-11-191098v1 114/7/1383    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 Ansari, M. Articles by Krajinovic, M. Search for Related Content PubMed PubMed Citation Articles by Ansari, M. Articles by Krajinovic, M. Related Collections Lymphoid Neoplasia Brief Reports Clinical Trials and Observations Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Brief Report Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia Marc Ansari1,2, Géraldine Sauty1, Malgorzata Labuda1, Vincent Gagné1, Caroline Laverdière1,3, Albert Moghrabi1,3, Daniel Sinnett1,3, and Maja Krajinovic1,3,4 1 Research Center, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC; 2 Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland; and Departments of 3 Pediatrics and 4 Pharmacology, University of Montreal, Montreal, QC Methotrexate and 6-mercaptopurine, important components of acute lymphoblastic leukemia treatment, are substrates for multidrug resistance-associated protein MRP4. Eight single nucleotide polymorphisms were analyzed in MRP4 gene, and 4 variants were identified as tagSNPs with frequency more than or equal to 5%. They were investigated for association with treatment responses in 275 children with acute lymphoblastic leukemia. The TC genotype of the regulatory T-1393C polymorphism was associated with better event-free survival (P = .02) and lower methotrexate plasma levels (P = .01). The CA genotype of A934C (Lys304Asn) substitution correlated in contrast with lower event-free survival (P = .02) and higher frequency of high-grade thrombocytopenia (P = .01). Gene reporter assay showed that the promoter haplotype uniquely tagged by the C-1393 allele conferred higher promoter activity compared with remaining haplotypes (P < .001). Further analyses are needed to replicate this pilot study and get closer insight into the functional effect of these polymorphisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Multidrug resistance–associated protein 4 (MRP4) gene polymorphisms and treatment response in adult acute lymphoblastic leukemia Monika Brüggemann, Heiko Trautmann, Dieter Hoelzer, Michael Kneba, Nicola Gökbuget, and Thorsten Raff Blood 2009 114: 5400-5401. [Full Text] [PDF] Response: MRP4 gene polymorphisms and treatment response in adult ALL Maja Krajinovic, Marc Ansari, and Daniel Sinnett Blood 2009 114: 5401-5402. [Full Text] [PDF] This article has been cited by other articles: M. Bruggemann, H. Trautmann, D. Hoelzer, M. Kneba, N. Gokbuget, and T. Raff Multidrug resistance-associated protein 4 (MRP4) gene polymorphisms and treatment response in adult acute lymphoblastic leukemia Blood, December 17, 2009; 114(26): 5400 - 5401. [Full Text] [PDF] M. Krajinovic, M. Ansari, and D. Sinnett Response: MRP4 gene polymorphisms and treatment response in adult ALL Blood, December 17, 2009; 114(26): 5401 - 5402. [Full Text] [PDF]

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