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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4493-4498. Prepublished online as a Blood First Edition Paper on June 19, 2003; DOI 10.1182/blood-2002-11-3461. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3461v1 102/13/4493    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 Steinbach, D. Articles by Sauerbrey, A. Search for Related Content PubMed PubMed Citation Articles by Steinbach, D. Articles by Sauerbrey, A. Related Collections Hematopoiesis and Stem Cells Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype Daniel Steinbach, Susann Wittig, Gunnar Cario, Susanne Viehmann, Angelika Mueller, Bernd Gruhn, Ralf Haefer, Felix Zintl, and Axel Sauerbrey From the University of Jena, Children's Hospital, Jena, Germany; the Hannover Medical School, Children's Hospital, Hannover, Germany; and the University of Giessen, Children's Hospital, Giessen, Germany. The family of multidrug resistance-associated proteins (MRPs) belongs to the superfamily of adenosine triphosphate-binding-cassette (ABC) transporters, which have the ability to function as outward pumps for chemotherapeutic drugs and therefore might be involved in drug resistance. In this study the expression of the MRP2, MRP3, MRP4, MRP5, and SMRP genes was measured using TaqMan real-time polymerase chain reaction (PCR) in 103 children with previously untreated acute lymphoblastic leukemia (ALL) (precursor B-cell ALL [B-ALL], n = 71; T-cell ALL [T-ALL], n = 32). All 5 genes were expressed with a great variability. Only MRP3 expression was associated with a significantly worse prognosis (P = .008). The median expression of MRP3 was 10-fold higher in T-ALL than in precursor B-ALL (P < .001) and 4-fold higher in male patients than in female patients (P < .001). The prognostic impact of MRP3 was independent of immunophenotype or sex. Higher levels of MRP3 were found in patients with a poor in vivo response to prednisone, but this could not be confirmed in an independent case-control study (40 patients) for prednisone response. In healthy donors, the median expression of MRP4 was 4-fold higher in bone marrow and 8-fold higher in CD34+ stem cells compared with peripheral blood (P = .002). Our results suggest that MRP3 is involved in drug resistance in childhood ALL. It therefore represents an interesting target to overcome multidrug resistance. High levels of MRP3 could possibly be the reason for the poorer prognosis of male patients or patients who have T-ALL. Similar to other members of the family of ABC transporters, MRP4 seems to be a marker for immature stem cells. (Blood. 2003;102:4493-4498) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. van de Ven, R. Oerlemans, J. W. van der Heijden, G. L. Scheffer, T. D. de Gruijl, G. 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