This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benderra, Z. Articles by Legrand, O. Search for Related Content PubMed PubMed Citation Articles by Benderra, Z. Articles by Legrand, O.

MRP3, BCRP, and P-Glycoprotein Activities are Prognostic Factors in Adult Acute Myeloid Leukemia

Authors' Affiliations: ¹ Laboratoire Institut National de la Sante et de la Recherche Medicale (INSERM U736), Universitaire Paris 6 (UMR 736), ² Service d'Hématologie Biologique, ³ Département d'Hématologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, Paris, and ⁴ JE Onco-Pharmacologie, IFR53, UFR de Pharmacie, Reims Cedex, France

Requests for reprints: Ollivier Legrand, Département d'Hématologie, Hôpital Hôtel-Dieu, 1 Place du parvis, Notre Dame, 75004 Paris, France. Phone: 33-1-4234-8585; Fax: 33-1-4234-8406; E-mail: ollivier.legrand{at}htd.ap-hop-paris.fr.

Purpose: P-Glycoprotein (Pgp) is associated with poor outcome in acute myeloid leukemia (AML). We have investigated other ATP-binding cassette proteins such as BCRP, MRP1, MRP2, MRP3, and MRP5 for their potential implication in chemoresistance.

Experimental Design and Results: Eighty five AML patient samples were analyzed in this study. First, MRP3 function was higher in patients which had a high level of leukocytes (P = 0.01), a M5 FAB subtype (P = 0.04), and an intermediate or poor cytogenesis (P = 0.05). BCRP activity was not correlated with clinical or biological variables, but high Pgp activity was correlated with the following variables: CD34 expression (P = 0.002), FAB subtype (P = 0.002), intermediate or poor cytogenesis (P = 0.02), and elderly patients (P = 0.03). Second, Pgp, MRP3, and BCRP activities were correlated with complete remission (P = 0.02, P = 0.04, and P = 0.04, respectively), disease-free survival (P = 0.02, P = 0.03, and P = 0.25, respectively), and overall survival (P = 0.04, P = 0.04, and P = 0.05, respectively) in multivariate analysis. The patient samples expressing one or none of these Pgp, MRP3, or BCRP functional proteins have a better prognosis than the patients expressing two or three of these functional proteins (complete remission, P = 0.02; disease-free survival, P = 0.01; overall survival, P < 0.001).

Conclusions: BCRP and MRP3 may also be involved in chemoresistance in AML, especially MRP3 in patients with M5 FAB. Additional modulation of BCRP or MRP3 to Pgp modulation may be necessary in some patients in order to improve the treatment outcome.

This article has been cited by other articles:

				W. Fiskus, R. Rao, P. Fernandez, B. Herger, Y. Yang, J. Chen, R. Kolhe, A. Mandawat, Y. Wang, R. Joshi, et al. Molecular and biologic characterization and drug sensitivity of pan-histone deacetylase inhibitor-resistant acute myeloid leukemia cells Blood, October 1, 2008; 112(7): 2896 - 2905. [Abstract] [Full Text] [PDF]

				C. J. Henrich, R. W. Robey, H. R. Bokesch, S. E. Bates, S. Shukla, S. V. Ambudkar, M. Dean, and J. B. McMahon New inhibitors of ABCG2 identified by high-throughput screening Mol. Cancer Ther., December 1, 2007; 6(12): 3271 - 3278. [Abstract] [Full Text] [PDF]

				C. Marzac, I. Teyssandier, O. Calendini, J.-Y. Perrot, A.-M. Faussat, R. Tang, N. Casadevall, J.-P. Marie, and O. Legrand Flt3 Internal Tandem Duplication and P-Glycoprotein Functionality in 171 Patients with Acute Myeloid Leukemia Clin. Cancer Res., December 1, 2006; 12(23): 7018 - 7024. [Abstract] [Full Text] [PDF]

				D. Steinbach, J.-P. Gillet, A. Sauerbrey, B. Gruhn, K. Dawczynski, V. Bertholet, F. de Longueville, F. Zintl, J. Remacle, and T. Efferth ABCA3 as a Possible Cause of Drug Resistance in Childhood Acute Myeloid Leukemia. Clin. Cancer Res., July 15, 2006; 12(14): 4357 - 4363. [Abstract] [Full Text] [PDF]