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Research Article

The Role of Drug Efflux Pumps in Acute Myeloid Leukemia

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Pages 685-701 | Published online: 01 Jul 2009

  • Abramson, S., Miller, R.G. and Phillips, R.A. (1977) "The identification in adult bone marrow of pluripotent and restricted stem cells of the mycloid and lymphoid systems", J. Exp. Med. 145, 1567-1579.
  • Melcalf, D. (19891 "The molecular control of cell division, differentiation commitment and maturation in haemopoictic cells", Nature 339, 27-30.
  • Ogawa, M., Porter, PN and Nakahata, T. (1983) "Renewal and commitment to differentiation of hemopoietic stem cells (an interpretive review)", Blood 61, 823-829.
  • Harrison, D.E. and Zhong, R.K. (1992) "The same exhaustible multilineage precursor produces both myeluid and lymphoid cells as early as 3-4 weeks after marrow transplantation", Proc. Natl Acad. Sci. USA 89, 10134-10138.
  • Knapp, W., Strobl, H., Schcinecker, C., Bello-Fernandez. C and Majdic, O. (1995) "Molecular characterization of CD34+ human hematopoietic progenitor cells", Ann. Hematol. 70, 281-296.
  • Gallacher, L., Murdoch, B., Wu, D.M., Karanu, EN., Keeney, M. and Bhatia. M. (2000) "Isolation and characterization of human CD34 ()Lin(-) and CD34(+)Lin(- ) hematopoietic stem cells using cell surface markers ACI33 and CD7", Blood 95, 2813-2820.
  • Ploemacher, R.E. and Brons, N.H. (1988) "Cells with marrow and spleen repopulating ability and forming spleen colonies on day 16, 12, and 8 are sequentially ordered on the basis of increasing rhodamine 123 retention", J. Cell Physiol. 136, 531-536.
  • Mulder, A.H. and Visser, J.W. (1987) "Separation and functional analysis of bone marrow cells separated by rhodamine-123 fluorescence", Exp. Hematol. 15, 99-104.
  • Lampidis, T.J., Munck, J.N., Krishan, A. and Tapiero, H. (1985) "Reversal of resistance to rhodamine 123 in adriamycin-resislant Friend leukemia cells", Cancer Res. 45, 2626-2631.
  • Neyfakh, A.A. (1988) "Use of fluorescent dyes as molecular probes for the study of multidrug resistance", Exp. Cell Res. 174, 168-176.
  • Chaudhary, P.M. and Roninson, I.B. (1991) "Expression and activity of P-glycuprotein, a multidrug efflux pump, in human hematopoietic stem cells", Cell 66, 85-94.
  • Bunting, K.D., Galipeau, J., Topham, D., Benaim, E. and Sorrentino, B.P. (1998) "Transduction of murine bone marrow cells with an MDRI vector enables ex vivo stem cell expansion, hut these expanded grafts cause a myeloproliferative syndrome in transplanted mice", Blood 92, 2269-2279.
  • Bunting, K.D., Zhou, S., Lu, T. and Sorrentino, B.P. (2000) "Eaforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo", Blood 96, 902-909.
  • Schiedlmeier, B., Kuhlcke, K., Eckert, H.G., Baum, C. Zeller, W.J. and Fruehauf, S. (2000) "Quantitative assessment of retroviral transfer of the human multidrug resistance 1 gene to human mobilized peripheral blood progenitor cells engrafted in nonobese diabetic/severe combined immunodeficient mice", Blood 95, 1237-1248.
  • Doyle, L.A., Yang, W., Abruzzo, L.V, Krogmann, T., Gao, Y. Rishi, A.K. and Ross, D.D. (1998) "A multidrug resistance transporter from human MCF-7 breast cancer cells", Proc. Natl Acad. Sci. USA 95, 15665-15670.
  • Scharenberg, C.W., Harkey, M.A. and Torok-Storb, B.J. (2000) "The transporter ABCG2 effluxes Hoechst and its expression is restricted to the most primitive human hcmatopoietic cells", Blood 96, 666a.
  • Zhou, S., Morris, J.J., Bunting, K.D., Osawa, M., Schuetz, J.D., Nakauchi, H. and Sotrentino, B.P. (2000) "Expression of the breast cancer resistance protein (BCRP) in side population (SP) stem cells, natural killer (NK) lymphocytes, and crythroid progenitor cells", Blood 96, 820a.
  • Zhou, S., Schuetz, J.D., Bunting, K.D., Colapietro, A.M. Sampath, J., Morris, J.J., Lagutina, I. Grosveld, G.C., Osawa, M., Nakauchi, H. and Sorrentino. B.P. (2001) "The ABC transporter Bcrpl/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype", Nat. Med. 7, 1028-1034.
  • Bennett, J.M., Catovxky, D., Daniel, M.T., Flandrin, G., Galton, D.A., Gralnick, H.R. and Sultan, C. (1976) "Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group", Br. J. Huematol. 33, 451-458.
  • Bennett, J.M., Catovsky, D., Daniel, M.T., Flandrin, G., Gallon. D.A., Gralnick, H.R. and Sultan, C. (1985) "Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French American-British cooperative group", Ann. Intern Med. 103, 620-625.
  • Lowenberg, B., Suciu, S., Archimbaud, E., Haak, H., Stryckmans, P., Je Cataldo, R., Dekker, A.W., Berneman, Z.N., Thyss. A., van der Lelie, J, Sonneveld, P., Visani, G., Fillet, G., Hayat, M., Hagemeijer, A., Solbu, G. and Zittoun, R. (1998) "Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group", J. Clin. Oncol. 16, 872-881.
  • Vellenga, E., van Putten, W.L., Boogaerts, M.A., Daenen, S.M., Verhoef, G.E., Hagenbeek. A., Jonkhoff, A.R., Huijgens, P.C., Verdonck, L.F., van der Lelie, J., Scheuten, H.C., Gmur, J., Wijermans, P., Gratwohl, A., Hess, U., Fey, M.F. and Lowenberg. B. (1999) "Peripheral blood stem cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia?", Bone Morrow Transplant. 23, 1279-1282.
  • Bishop, J.F., Matthews. J.P., Young, G.A., Szer, J., Gillett, A., Joshua, D., Bradstock, K., Enno. A., Wolf, M.M. and Fax, R. (1996) "A randomized study of high-dose cytarabine in induction in acute myeloid leukemia", Blood 87, 1710-1717.
  • Weick, J.K., Kopecky, K.J., Appelbaum, F.R., Head, D.R., Kingsbury, I.,L., Balcerzak, S.P., Bickers, J.N., Hynes. HE., Welbom, J.I., Simon, S.R. and Grever, M. (1996) "A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute mycloid leukemia: a Southwest Oncology Group study", Blood 88, 2841-2851.
  • Bradley, G., Juranka, PF. and Ling. V. (I988) "Mechanism of multidrug resistance", Biochem. Biophys. Acta 948, 87-128.
  • Peters, W.H. and Roelofs, H.M. (1992) "Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco2 human colon adenocarcinoma cells: a possible role for glutathione S-transferases", Cancer Res. 52, 1886-1890.
  • Meijer, C., Mulder, N.H., Timmer-Bosscha, H., Sluiter, W.J., Meersma, G.J. and de Vries, E.G (1992) "Relationship of cellular glutathione to the cytotoxicity and resistance of seven platinum compounds", Cancer Res. 52, 6885-6889.
  • Tew, K.D. (1994) "Glutathione-associated enzymes in anticancer drug resistance", Cancer Res. 54, 4313-4320.
  • Pommier, Y., Kerrigan, D., Schwartz. R.E., Swack, J.A. and McCurdy. A. (1986) "Altered DNA topoisomerase Il activity in Chinese hamster cells resistant to topoisomerase Il inhibitors", Cancer Res. 46, 3075-3081.
  • Chin, J.E., Soffir, R., Noonan, K.E., Choi, K. and Roninson, I.B. (1989) "Structure and expression ol the human MDR (P-glycoprotein) gene family", Mol. Cell Biol. 9, 3808-3820.
  • Higgins, C.F. (1994) "Flip-flop: the transmembrane translocation of lipids", Cell 79, 393-395.
  • Bolhuis, H., van Veen, H.W., Poolman, B., Driessen, A.J. and Konings, W.N. (1997) "Mechanisms of mullidrug transporters", FEMS Microbiol. Rev. 21, 55-84.
  • Pastan, I., Goltesman, M.M., Ueda, K., Lovelace, L., Rutherford. A.V. and Willingham, M.C. (1988) "A retrovirus carrying an MDRl cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells", Proc. Natl Acad. Sci. USA 85, 4486-4490.
  • Hait, W.N., Choudhury, S., Srimatkandada, S. and Murren, J.R. (1993) "Sensitivity of K562 human chronic myelogenous leukemia blast cells transfected with a human multidrug resistance cDNA to cytotoxic drugs and differentiating agents", J. Clin. Invest. 91, 2207-2215.
  • Hoffmeyer, S., Burk, O., von Richter. O., Arnold, H.P., Brockmoller, J., Johne, A., Cascorbi. I., Gerloff, T., Roots. I., Eichelbaum, M. and Brinkmann, U. (2000) "Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo", Proc. Natl Acad. Sci. USA 97, 3473-3478.
  • Cascorbi, I., Gerloff, T., Johne, A., Meisel, C., Hoffmeyer, S-, Schwab, M., Schaeffeler, E., Eichelbaum, M. Brinkmann, U. and R00ts, 1. (2001) "Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDRI gene in white subjects", Clin. Pharmacol. Ther. 69, 169-174.
  • Rao, V.V., Dahlhcimer, J.L., Bardgett, M.E., Snyder, A.Z., Finch, R.A., Sartorelli, A.C. and Piwnica-Worms. D. (1999) "Choroid plexus epithelial expression of MDRl P-glycoprotein and multidrug resistance-associated protein contribute to the bloodcerebruspinal-fluid drug-permeability hairier", Proc:. Natl Acad. Sci. USA 96, 3900-3905.
  • Wijnholds, J., de Lange, E.C., Scheffer, G.L., van den Berg, D.J., Mol. CA., van der Valk, M., Schinkel, A.H., Scheper, R.J., Breimer, D.D and Borst, P. (2000) "Multidrug resistance protein I protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier", J. Clin Invest. 105, 279-285.
  • Smit, J.W., Huisman, M.T., van Tellingen, O., Wiltshire, H.R. and Schinkel, A.H. (1999) "Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure", J. Clin. Invest 104, 1441-1447
  • Ambudkar, S.V., Dey, S., Hrycyna, C.A., Ramachandra, M., Pastan. I. and Gottesman, M.M. (1999) "Biochemical, cellular, and pharmacological aspects of the multidrug transporter", Annu. Rev. Pharmacol. Toxicol. 39, 361-398.
  • Fojo. A.T., Ueda, K., Slamon, D.J., Poplack, D.G. Gottesman, M.M. and Pastan. I. (1987) "Expression of ¢ multidrug-resistance gene in human tumors and tissues", Proc. Natl Acad. Sci. USA 84, 265-269.
  • Neyfakh, A.A., Serpinskaya, A.S., Chervonsky, A.V., Apasov, S.G. and Kazarov, A.R. (1989) "Multidrug-resistancc phenotype of a subpopulalion of T-lymphocy[es without drug selection", Exp. Cell Res. 185, 496-505.
  • Smeels, M., Raymakcrs. R., Vierwiuden. G., Pennings, A., van de, L., L.,. Wessels, H., Boezeman, J. and dc Witte. T. (1997) "A low but functionally significant MDRI expression protects primitive haemopoietic progenitor cells from anthracycline toxicity", Br. J. Haematot. 96, 346-355.
  • Schueiz, E.G., Umbenhauer, D.R., Yasuda, K., Brimer, C., Nguyen, L., Relling, M.V., Schuetz, J.D. and Schinkel, A.H (2000) "Altered expression of hepatic cytochromes P-450 in mice deficient in one or more mdrI genes", Mol. Pharmacol. 57, 188-197.
  • Schinkel, A.H., Smit, J.J., van Tellingen, O., Beijnen, J.H., Wagenaar, E., van Deemter, L., Mol, C.A. van der Valk, M.A., Robanus-Maandag, E.C. and te Riele, H.P. (1994) "Disruption of the mouse mdrl a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs", Cell 77, 491-502.
  • Schinkel, A.H., Mayer, U., Wagenaar, E., Mol. C.A., van Deemter. L., Smit, J.J., van der Valk, M.A., Voordouw, A.C., Spits, H., van Tellingen, O., Zijlmans, J.M., Fibbe, W.E. and Borst, P. (1997) "Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-elycoproteins", Proc. Natl Acad. Sci. USA 94, 4028-4033.
  • Zhang, Z.J., Saito, T., Kimura, Y., Sugimoto, C., Ohtsubo, T. and Saito, H. (2000) "Disruption of mdr 1a P-glycoprotein gene results in dysfunction of blood inner car barrier in mice", Brain Res. 852, 116-126.
  • Johnson, D.R., Finch, R.A., Lin, Z.P., Zeiss, C.J. and Sartorelli, A.C. (2001) "The pharmacological phenotype of combined multidrug-resistance mdr 1a/1b- and mrpl-deficient mice", Cancer Res. 61, 1469-1476.
  • Allen, J.D., Brinkhuis, R.F., van Deemter, L., Wijnholds, J. and Schinkel, A.H. (2000) "Extensive contribution of the multidrug transporter). P-glycoprotein and Mrpl to basal drug resistance", Cancer Res. 60, 5761-5766.
  • Slovak, M.L., Hoeltge, G.A., Dalton, W.S. and Trent, J.M. (1988) "Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines", Cancer Res. 48, 2793-2797.
  • Scheper, R.J., Bulte J.W., Brakkee, J.G., Quak, J.J., van der, S.E., Balm, A.J., Meijer, C.J., Broxterman, H.J., Kuiper, C.M. and Lankelma, J. (1988) "Monoclonal antibody JSB-1 detects a highly conserved ecpitope on the P-glycoprotein associated with multidrug-resistajice", Int. J. Cancer 42, 389-394.
  • Hamada, H. and Tsuruo, T. (1986) "Functional role for the 170- to 180-kDa glycoprotein specific to drug- resistant tumor cells as revealed by monoclonal antibodies", Proc. Natl Acad Sci. USA 83, 7785-7789.
  • Mechetner, E.B. and Roninson, I.B. (1992) "Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody", Proc. Natl Acad. Sci. USA 89, 5824-5828.
  • Arceci, R.J., Stieglitz, K., Bras. J., Schinkel, A., Baas. F. and Croop, J. (1993) "Monoclonal antibody to an external epitope ut the human mdrl P-glycoprotein", Cancer Res. 53, 310-317.
  • Lehne, G., De Angelis, P., Clausen. O.P., Egeland, T., Tsuruo. T. and Rugstad, H.E. (1995) "Binding diversity of antibodies against external and interna] epitopes of the multidrug resistance gene product P-glycoprotein", Cytometry 20, 228-237.
  • Legrand, O., Perrot, J.Y., Simonin, G., Baudard, M. and Marie, J.P. (2001) "JC-1: a very sensitive fluorescent probe to test P-gp activity in adult acute mycloid leukemia", Blood 97, 502-508.
  • Wadkins, R.M. and Houghlon, P.J. (1995) "Kinetics of transport of dialkyloxacarbocyanines in multidrug-resistant cell lines overexpressing P-glycoprotein: interrelationship of dye alkyl chain length, cellular flux, and drug resistance", Hiochemistjy 34, 3858-3872.
  • Tsuruo, T., Iida, H., Tsukagoshi, S. and Sakurai, Y. (1981) "Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of virtcristine and vinblaxtine by verapamil", Cancer Res. 41, 1967-1972.
  • Cornwell, M.M., Pastan, I. and Gottesman, M.M. (1987) "Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding Io P-glycoprotetn", J. Biol. Chem. 262, 2166-2170.
  • te Boekhorst, P.A., van Kapel, J., Schoester, M. and Sonnevold. P. (1992) "Reversal of typical multidrug resistance by cyclosporin and its non- immunosuppressive analogue SDZ PSC 833 in Chinese hamster ovary cells expressing the mdr1 phenotype", Cancer Chemother. Pharmacol. 30, 238-242.
  • Hyafil, K. Vergely, C., Du, V.P and Grand-Perrel, T. (1993) "In vitro and in vivo reversal of multidrug resistance by GFl20918. an acridonecarboxanide derivative", Cancer Res. 53, 4595-4602.
  • Evers, R., Kool, M., Smith, A.J., van Deemter, L., de Haas. M. and Borst, P. (2000) "Inhibitory effect of the reversal agents V-104. GF120918 and Pluronic L61 on MDR1 Pgp-", Br. J. Cancer 83, 366-374.
  • Venne, A., Li, S., Mandeville, R., Kabanov, A. and Alakhov, V. (1996) "Hypersensitizing effect of pluronic L61 on cytotoxic activity, transport, and suhcellular distribution of doxorubicin in multiple drug-resistant cells", Cancer Res 56, 3626-3629.
  • Glioiak, B. and Le, T. (1999) "Tumor necrosis factor-related apoptosis-inducing ligand's antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11", Cancer Res. 59, 6153-6158.
  • Mistry, P., Stewart. A.J., Dangerfield, W., Okiji. S. Liddle. C., Bootle, D., Plumb. J.A., Templeton, D. and Charlton, P. (2001) "In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator XR9576", Cancer Res. 61, 749-758.
  • Broxterman, H.J., Sunneveld, P., Feller. N., Ossenkoppele, G.J., Wahrer, D.C., Eekman, C.A. Schoester, M., Lankelma, J., Pinedo. H.M., Lowenberg, B. and Schuurhuis, G.J. (1996) "Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity", Blood 87, 4309-4816.
  • Tafuri, A., Sommaggio, A., Burba, L., Albergoni, M.P., Petrucci, M.T., Mascolo, M.G., Testi, A.M. and Basso, G. (1995) "Prognostic value of rhodamine-efflux and MDR-I/P-I70 expression in childhood acute leukemia", Leuk Res. 19, 927-931.
  • Feller, N., Kuiper, C.M., Lankelma, J., Ruhdal, J.K., Scheper, R.J., Pinedo, H.M. and Broxterman, H.J. (1995) "Functional detection of MDRI/PI70 and MRP/P190-mediated multidrug resistance in tumour cells by flow cytometry", Br. J Cancer 72, 543-549.
  • Marie, J.P., Ziltoun, R. and Sikic, B.I. (1991) "Multidrug resistance (mdrl) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity",Blood 78, 586-592.
  • Pirker, R., Wallner, J., Geissler, K., Linkesch, W., Haas, O.A., Bettelheim, P., Hopfuer, M., Scherrer, R., Valent, P. and Havelec, L. (1991) "MDRl gene expression and treatment outcome in acute myeloid leukemia", J. Natl Cancer Inst. 83, 708-712.
  • Campos, L., Guyotat, D., Archimbaud, E., Calmard-Oriol, P., Tsuruo, T. Troney, J., Treille, D. and Fiere, D. (1992) "Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis", Blood 79, 473-476.
  • Leith, C.P., Kopecky, K.J., Chen, I.M., Eijdems, L., Slovak, M.L., McConnell, T.S., Head, D.R., Weick, J., Grever, M.R., Appelbaum, F.R. and Willman, C.L. (1999) "Frequency and clinical significance of the expression of the multidrug resistance proteins MDRI/P-glycoprotein. MRPI. and LRP in acute myeloid leukemia: a Southwest Oncology Group Study", Blood 94, 1086-1099.
  • Marie, J.P., Zhou, D.C., Gurbuxani, S., Legrand, O. and Zitoun, R. (1996) "MDRI/P-glycoprotein in haematological neoplasms", Eur. J. Cancer 32A, 1034-1038.
  • te Boekhorst, P.A., de Leeuw, K., Schoester, M., Wittebol, S., Nooter, K., Hagemeijer, A., Lowenberg, B. and Sonneveld, P. (1993) "Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+ acute myeloid leukemia cells", Blood 82, 3157-3162.
  • Drenou, B., Fardel, O., Amiot, L., and Fauchet, R. (1993) "Detection of P-glycoprotein activity on normal and leukemic CD34+ cells", Leak. Res. 17, 1031-1035.
  • van der Kolk, D.M., de Vries, E.G.E., Noordhoek, L., van den Berg, F., van der Pol. M.A., Muller, M. and Vellenga, E. (2001) "Activity and expression of the multidrug resistance proteins P-glycoprotein, MRP1, MRP2, MRP3 and MRP5 in de novo and relapsed acute myeloid leukemia", Leukemia 20O1 15:1544-53.
  • Borg, A.C., Burgess, R., Green. L.M., Scheper, R.J. und Yin, J.A. (1998) "Overexpression of lung-resistance protein and increased P-glycoprotein function in acute myeloid leukaemia cells predict a poor response to chemotherapy and reduced patient survival", Br. J. Haematol. 103, 1083-1091.
  • Zochbauer, S., Gsur, A., Brunner, R., Kyrie. P.A., Lechner, K. and Pirker, R. (1994) "P glycoprotein expression as unfavorable prognostic factor in acute myeloid leukemia", Leukemia 8, 974-977.
  • Leith, C.P., Kopecky, K.J., Godwin. J., McConnell, T., Slovak, M.I., Chen, I.M., Head, D.R., Appelbaum, F.R. and Willman,C.L. (1997) "Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDRI) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study", Blood 89, 3323-3329.
  • Del Poeta, G., Venditti, A., Stasi, R., Aronica, G., Cox, M.C., Buccisano, F., Tamburini, A., Bruno. A., Maurillo, I., Battaglia, A., Suppo, G., Epiceno, A.M., Del Moro, B., Masi, M., Amadori, S. and Papa, G. (1999) "P-glycoprotein and terminal transferase expression identify prognostic subsets within cytogenetic risk classes in acute myeloid leukemia", Leuk. Res. 23, 451-465.
  • Michieli, M., Datniani, D., Ermacora, A., Masolini, P., Raspadori, D., Visani, G., Scheper, R.J. and Baccarani, M. (1999) "P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: biological and clinical implications", Br. J. Haematol. 104, 328-335.
  • Wuchter, C., Leonid, K., Ruppert, V., Schrappe, M., Buchner, T., Schoch, C. Haferlach, T., Harbott, J., Ratei, R., Dorken, B. and Ludwig, W.D. (2000) "Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia", Haematologica 85, 711-721.
  • Lyttelton, M.P., Hart, S., Guneshaguru, K., Hoffbrand, A.V. and Mehta, A.B. (1994) "Quantitation of multidrug resistant MDR1 transcript in acute myeloid leukaemia by non-isotopic quantitative cDNA-polymerase chain reaction", Br. J. Haematol. 86, 540-546
  • Wood, P., Burgess, R., MacGregor, A. and Yin, J.A. (1994) "P-glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival", Br. J. Haematol. 87, 509-514.
  • Maslak, P., Hegewisch-Becker, S., Godfrey, L. and Andreeff, M. (1994) "How cytometric determination of the multidrug-resistant phenotype in acute leukemia", Cytometry 17, 84-93.
  • Zhou, D.C., Zittoun, R. and Marie, J.P. (1995) "Expression of multidrug resistance-associated protein (MRP) and multidrug resistance (MDRI) genes in acute myeloid leukemia", Leukemia 9, 1661-1666.
  • Ino T., Miyazaki, H., Isogai, M., Nomura, T., Tsuzuki, M., Tsuruo. T., Ezaki, K. and Hirano, M. (1994) "Expression of P-glycoprotein in de novo acute myelogenous leukemia at initial diagnosis: results of molecular, and functional assays, and correlation with treatment outcome", leukemia 8, 1492-1497.
  • List, A.F. (1996) "Role of multidrug resistance and its pharmacological modulation in acute myeloid leukemia", Leukemia 10, 937-942.
  • Heuvel-Eibrink, M.M., Wiemer, E.A., de Boevere, M.J., van der Holt, B., Vossebeld, P.J., Pieters, R. and Sonneveld, P. (2001)"MDRI gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia", Blood 97, 3605-3611.
  • Baer, M.R., Stewart, C.C., Dodge, R.K. Leget, G., Sule, N., Mrozek, K., Schiffer, C.A., Powell, B.L., Kolitz, J.E., Moore, J.O., Stone, R.M., Davey, F.R., Carroll, A.J., Larson, R.A. and Bloomfield, C.D. (2001) "High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361)", Blood 97, 3574-3580.
  • Lee, K.J., George, S.L., Caligiuri, M., Szatrowski, T.P., Powell, B.L., Lemke, S., Dodge. R.K., Smith, R., Baer, M. and Schiffer. C.A. (1999) "Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of cancer and leukemia group B study 9420", J. Clin. Oncol. 17, 2831-2839.
  • List, A.F., Spier, C., Greer, J., Wolff, S., Hutter, J., Dorr, R., Salmon, S., Futscher, B., Baier, M. and Dulton, W. (1993) "Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia", J. Clin. Oncol. 11, 1652-1660.
  • Yahanda, A.M., Alder, K.M., Fisher, G.A., Brophy, N.A., Halsey. J., Hardy, R.I., Gosland, M.P., Lum, B.L and Sikic, B.I. (1992) "Phase I trial of etoposide with cyclosporine as a modulator of multidrug resistance", J. Clin. Oncol. 10, 1624-1634.
  • Tidefelt U., Lilieinark, J., Grober. A., Liliemark, E., SundmanEngberg, B., Juliusson, G., Stenke, L., Elmhom-Rosenborg, A., Mollgard, L., Lehman. S., Xu, D., Covelli, A., Gustuvsson, B. and Paul, C. (2000) "P-Glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of daunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia", J. Clin. Oncoi 18, 1837-1844.
  • Advani, R., Saba, H.I., Tallman, M.S., Rowe, J.M., Wiernik, P.H., Ramek, J., Dugan, K., Lum, B., Villena, J., Davis, E., Paietta, E., Litchman, M., Sikie, B.I. and Greenberg, P.L. (1999) "Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar)", Blood 93, 787-795.
  • Solary, E., Witz, B., Caillot, D., Moreatt, P., Desablens, B., Cahn. J.Y., Sadoun. A., Pignon, B., Berthou, C., Muloisel, F., Guyotat, D., Casassus, P., Ifrah, N., Lamy, Y., Audhuy, B., Colombat, P. and Harousseau, J.L. (1996) "Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukcmias: a randomized multicenter study", Blood 88, 1198-1205.
  • Greenberg, P., Advani, R., Tallman, M., Letendre, L., Saba, H. Dugan, K., Lee, S.J., Lum, B., Sikic, B.L. Paietta, E., Bennett, J. and Rowe, J.M. (1999) "Treatment of refractory/relapsed AML with PSC833 plus mitoxantrone, etoposide. cytarabine (PSC-MEC) vs. MEC: randomized phase Ill trial (E2995)", Blood 94. 383a.
  • Baer, M.R., George, S.L., Dodge, R.K., Cooke, K., Caligiuri, M., Powell, B.L., Kolitz, J.E., Schiffer, C.A. and Larson, R.A. (1999) "Phase III study of PSC-833 modulation of multidrug resistance (MDR) in previously untreated acute myeloid leukemia (AML) patiems (pts) > 60 years (CALBG9720)", Blood 94, 383a.
  • Smyth, M.J., Krasovskis, E., Sutton, V.R. and Johnstone, R.W. (1998) "The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase dependent apoptosis", Proc. Natl Acad. Sci. USA 95, 7024-7029.
  • Johnstone, R.W., Cretney E. and Smyth, M.J. (1999) "P-glyco protein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death", Blood 93, 1075-1085.
  • Robinson, L.J., Roberts, W.K., Ling, T.T., Lamming. D., Sternberg, S.S. and Roepe, P.D. (1997) "Human MDRI protein overexpression delays the apoptotic cascade in Chinese hamster ovary fibroblasts", Biochemistry 36, 11169-11178.
  • Ruefli, A.A., Smyth, M.J. and Johnstone, R.W. (2000) "HMBA induces activation of a caspase independent cell death pathway to overcome P-glycoprotein-mediated multidrug resistance", Blood 95, 2378-2385.
  • Dokter, W.H., Tuyt, L., Sierdsema, S.J., Esselink, M.T. and Vellenga, E. (1995) "The spontaneous expression of interleukin-1 beta and intcrleukin-6 is associated with spontaneous expression of AP-1 and NF-kappa B transcription factor in acute myeloblastic leukemia cells", Leukemia 9, 425-432.
  • Thevenod, F., Friedmann, J.M., Katsen, A.D. and Hauser, I.A. (2000) "Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappa B activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis", J. Biol. Chem. 275, 1887-1896.
  • van Helvoort, A., Smith, A.J., Sprang, H., Fritzsche, I., Schinkel, A.H., Borst, P. and van Meer, G. (1996) "MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine", Cell 87, 507-517.
  • Bezombes, C., Macstre, N., Laurent, G. Levade, T., Bettaieh, A. and Jaffrezou, J.P. (1998) "Restoration of TNF-alpha-induced ceramide generation and apoptosis in resistant human leukemia KGIa cells by the P-glycoprotein blocker PSC833", FASEB J. 12, 101-109.
  • Pallis, M. and Russell, N. (2000) "P-glycoprotein plays a drugefflux-independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modulation of a sphingomyelin-ceramide apoptotic pathway", Blood 95, 2897-2904.
  • Drach, J., Gsur, A., Hamilton, G., Zhao, S., Angerler, J., Fiegl, M., Zojer, N., Raderer, M., Haberl, I., Andreeff, M. and Huber, H. (1996) "Involvement of P-glycoprotein in the transmembrane transport of mterleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes", Blood 88, 1747-1754.
  • Cullis, P.R, Hope, M.J., Bally, M.B., Madden, T.D., Mayer, L.D. and Fenske, D.H. (1997) "Influence ot pH gradients on the transbilayer transport of drugs, lipids. peptides and metal ions into large unilamellar vesicles", Biochim. Biophys. Acta 1331, 187-211.
  • Stennicke, H.R. and Salvesen, G.S. (1997) "Biochemical characteristics of caspases-3. -6. -7. and -8", J. Biol. Chem. 272, 25719-25723.
  • Goltlieb, R.A., Nordberg, J. Skowronski, K. and Babior, B.M. (1996) "Apoptosis induced in Jurkal cells by several agents is preceded by intracellular aciditication", Proc. Natl. Acad. Sci. USA 93, 654-658.
  • Mirski, S.E., Gerlach, J.H and Cole, S.P. (1987) "Multidrug resistance in a human small cell lung cancer cell line selected in adriamyein", Cancer Res. 47, 2594-2598.
  • McGrath, T. and Center, M.S. (1987) "Adriamycin resistance in HL60 cells in the absence of detectable P-glycoprotein", Biochem. Biophys Cononun. 145, 1171-1176.
  • Cole, S.P. Bhardwaj, G., Gerlach, J.H., Mackie, J.E., Grant, C.E., Almquist, K.C., Stewart, A.J., Kurz, E.U., Duncan, A.M. and Deeley, R.G. (1992) "Overespression of a transporter gene in a multidrug-resistant human lung cancer cell line", Science 258, 1650-1654
  • Paul, S., Breuninger, L.M., Tew, K.D., Shen, H. and Kruh, G.D. (1996) "ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles establishes MRP as a broad specificity transporter", Proc. Natl Acad. Sci. USA 93, 6929-6934.
  • Marbeul-Gueye, C., Broxiemian, H.J., Dubru, K. Priebe, W. and Garnier-Suillerot, A. (1998) "Kinetics of anthracycline efflux from multidrug resistance protein-expressing cancel cells compared with P-glycoprotein-expressing cancer cells", Mol. Pharmacol. 53, 141-147.
  • Loe, D.W., Almquist, K.C., Deeley, R.G. and Cole, S.P. (1996) "Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-depeudent vincristine transport", J Biol. Chem. 271, 9675-9682.
  • Renes, J., de Vries, E.G., Nienhuis, E.F., Jansen, P.L. and Muller, M. (1999) "ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRPI", Br. J. Pharmacol. 126, 681-688.
  • Muller, M. Meijer, C. Zaman, G.J., Borst, P., Scheper, R.J. Mulder, N.H., de Vries, F.G. and Jansen, P.I., (1994) "Overexpression of the gene encoding the multidrug resistanceassociated protein results in increased ATP dependent glutathione S-conjugate transport", Proc. Natl Acad. Sci. USA 91, 13033-13037.
  • Cole, S.P. and Deeley, R.G. (1998) "Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP", Bioessays 20, 931-940.
  • Grant, C.E., Valdimarsson, G., Hiplner, D.R., Almquist. K.C., Cole, S.P. and Deeley, R.G. (1994) "Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs", Cancer Res. 54, 157-161.
  • Zaman, G.J., Hens, M.J., van Leusden, M.R., de Haas, M., Mulder, H.S., Lankelma, J., Pinedo, H.M., Seheper, R.J., Baas, F. and Broxterman, H.J. (1994) "The human multidrug resistanceassociated protein MRP is a plasma membrane drug-efflux pump", Proc. Natl Acad. Sci. USA 91, 8822-8826.
  • Cole, S.P. Sparks, K.E., Fraser, K., Loe, D.W., Grant, C.F., Wilson, G.M. and Deeley, R.G. (1994) "Pharmacological characterization of multidrug resistant MRP transfected human tumor cells", Cancer Res. 54, 5902-5910.
  • Zhang, D.W., Cole, S.P. and Deeley, R.G. (2001) "Identification of an amino acid residue in multidrug resistance protein l critical for conferring resistance to anthracyclines", J Biol. Chem. 276, 13231-13239.
  • Leter, I., Jedlitschky, G., Buchholz., U., Cole, S.P. Deeley, R.G. and Keppler, D. (1994) "The MRP gene encodes an ATP-dependent export pump for lcukotriene C4 and structurally related conjugates", J. Biol. Chem 269, 27807-27810.
  • Ito, K., Olsen, S.l., Qiu, W., Deeley, R.G. and Cole, S. P. (2001) "Mutation of a single conservcd tryptophan in multidrug resistance protein 1 (MRPI/ABCCI) results in loss of drug resistance and selective loss of organic anion transport", J. Biol. Chem. 276, 15616-15624.
  • Hens, M.J., Zaman, C.J., van d., V., Izquierdo, M.A., Schroeijers. A.B., Scheffer, G.I., van der. G.P., de Has, M., Meijer, C.J. and Stheper, R.J. (1996) "Tissue distribution of the multidrug resistance protein", Am. J. Pathol. 148, 1237-1247.
  • Lorico, A. Rappa, G., Finch, R.A. Yang, D. Flavell, R.A and Sartorelli, A.C. (1997) "Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione", Cancer Res. 57, 5238-5242.
  • Wijnholds, J., Evers, R., van Leusden, MR., Mol. C.A., Zaman, G.J., Mayer, U., Beijnen, J.H., van der Valk. M., Krumpenfort, P and Borst, P. (1997) "Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein", Nat. Med. 3, 1275-1279.
  • Robbiani, D.F., Finch, R.A., Jager, D., Muller, W.A., Sartorelli, A.C. and Randolph, G.J. (2000) "The leukotriene C(4) transporter MRP1 regulates CCI. 19 (MIP-3beta ELC)-dependent mobilization of dendritic cells to lymph nodes", Cell 103, 757-768.
  • Wijnholds, J., Schoffer, G.L., van der Valk, M., van der Valk. P., Buijnen, J. H., Scheper, R.J. and Borst, P. (1998) "Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug induced damage", J. Exp. Med. 188, 797-808.
  • Flens, M.J., Izquierdo, M.A., Scheffer, G.L., Fritz. J.M., Meijer, C.J., Scheper, R.J. and Zaman, G.J (1994) "Immunochemical detection of the multidrug resistance-associated protein MRP in human multidrug-resislant tumor cells by monoclonal antibodies", Cancer Res. 54, 4557-4563.
  • Hooijberg, J.H., Broxterman, H.J., Scheffer, G.L., Vrasdonk, C., Heijn, M., de Jong, M.C., Scheper, R.J., Lankelma, J and Pinedo, H.M. (1999) "Potent interaction of flavopiridol with MRPI", Br. J. Cancer 81, 269-276.
  • Hipfner, D.R., Gauldie, S.D., Deeley, R.G. and Cole. S.P. (1994) "Detection of the M(r) 190,000 multidrug resistancc protein. MRP, with monoclonal antibodies", Cancer Res. 54, 5788-5792.
  • Feller, N., Bioxterman, H.J., Wahrer, D.C. and Pinedo, H.M. (1995) "ATP-dependent efflux of calcein by the multidrug resistance protein (MRP): no inhibition by intracellular glutathione depletion", FEBS Lett 368, 385-388.
  • van der Kolk, D.M., de Vries, E.G.H., Koning, J.A., van den Berg. E., Muller, M. and Vellenga, E. (1998) "Activity and expression of the multidrug resistance proteins MRP1 and MRP2 in acute mycloid leukemia cells, tumor cell lines, and normal bematopoielic CD34+ peripheral blood cells", Clin. Cancer Res 4, 1727-1736.
  • Gekeler, V. Boer, R., Ise, W. Sanders, K.H., Schachtele, C. and Beck, J. (1995) "The specific bisitidoiylmaleimide PKC-inhibitor GF 109203X efficiently modulate. MRP-associated multiple drug resistance", Biochem. Biophys. Res. Commun. 206, 119-126.
  • Jones, T.R., Zamboni, R., Belley, M. Champion, E., Charette, L., Ford-Hutchinson, A.W., Frenette, R., Gauthier, J.Y., Leger, S. and Masson, P. (1989) "Pharmacology of L-660, 711 (MK-571): a novel potent and selective Ieukotriene D4 receptor antagonist", Can. J. Physiol. Pharmacol 67, 17-28.
  • Homolya, L. Hollo, Z., Germanu, U.A. Pastan, I., Gottesman, M.M. and Sarkadi, B. (1993) "Fluorescent cellular indicators are extruded by the multidrug resistance protein", J. Biol. Chem. 268, 21493-21496.
  • Versantvoort, C.H., Schuurhuis, G.J., Pinedo, H.M., Eekman, C.A., Kuiper, C.M., Lankelma, J. and Broxterman. H.J. (1993) "Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells", Br. J. Cancer 68, 939-946
  • Shudo, N., Mizopuchi, T., Kiyosue, T. Arita, M., Yoshimura, A., Seto, K., Sakoda, R. and Akiyama, S. (1990) "Two pyridine analogues with more effective ability to reverse multlidrug resistance and with lower calcium channel blocking activity than their dihydropyridine counterparts", Cancer Res. 50, 3055-3061.
  • Hart, S.M., Ganeshaguru, K., Hoffbrand, A.V., Prentice. H.G. and Mehta, A.B. (1994) "Expression of the multidrug resistanceassociated protein (MRP) in acute leukaemia", Leukemia B, 2163-2168.
  • Schuurhuis, G.J., Bruxterman, H.J., Ossenkoppele. G.J., Baak, J.P., Eekman, C.A., Kuiper, C.M., Feller, N., van Heijningen, T.H., Klumper, E. and Pieters, R. (1995) "Functional multidrug resistance phenotype associated with combined overexpression of PgpMDR1 and MRP together with 1-beta-D-arabinofuranosylcytosine sensitivity may predict clinical response in acute myeloid leukemia", Clin. Cancer Res. 1, 81-93
  • Legrand, O., Perrot, J.Y., Tang, R., Simonin, G., Gurbuxani, S., Zitloun, R. and Marie, J.P. (1996) "Expression of the multidrug resistance-associated protein (MRP) mRNA and protein in normal peripheral blood and bone marrow haemopoietic cells", Br. J. Haematol. 94, 23-33.
  • Ross, D.D., Doyle, L.A., Schiffer, C.A., Lee, F.J., Grant, C.E., Cole, S.P. Deeley, R.G., Yang, W. and Tong, Y. (1996) "Expression of multidrug resistance-associated protein (MRP) mRNA in blast cells from acute myeloid leukemia (AML) patients", Leukemia 10, 48-55.
  • Xu, D., Knaust, E., Pisa, P., Palucka, K., Limdeberg, J., Arestrotn. I., Peterson, C. and Gruber, A. (1996) "Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation", Br. J. Haematol. 92, 847-854.
  • Filtpits, M., Suchomel, R.W., Zochbauer, S., Brunner, R., Lechner, K and Pirker, R. (1997) "Multidrug resistance-associated protein in acute myeloid leukemia: no impact on treatment outcome", Clin. Cancer Res. 3, 1419-1425.
  • Legrand, O., Simonin, G., Perrot, J.Y., Zittoun,R. and Marie, J.P. (1999) "Both Pgp and MRPI activities using calcein-AM contribute to drug resistance in AML", Adv Exp. Med. Biol. 457, 161-175.
  • van der Kolk, D.M., de Vries, E.G., van Putten, W.J., Verdonek. L.F., Ossenkoppele, G J., Verhoef, G.E. and Vellenga, E (2000) "P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia", Clin. Cancer Res. 6, 3205-3214.
  • Borg, A.G., Burgess, R., Green, L.M., Scheper, R.J. and Liu Yin. J.A. (2000) "P-glycoprotein and multidrug resistance-associated protein, but not lung resistance protein, lower the intracellular daunorubiein accumulation in acute myeloid leukaemic cells", Br. J. Haematol. 108, 48-54
  • Bailly, J.D., Muller, C. Jaffrezou, J.P., Demur, C., Gassar, G., Bordier, C. and Laurent, G. (1995) "Lack of correlation between expression and function of P-glycoprotein in acute myeloid leukemia cell lines", Leukemia 9, 799-807.
  • Leith, C.P., Chen, I.M., Kopecky, K.J., Appelhaum, E.R., Head, D.R., Godwin, J.E., Weick, J.K. and Willman, C.L. (1995) "Correlation of multidrug resistance (MDRI) protein expression with functional dye/drug efflux in acute myeloid leukemia by multiparameter flow cytometry: identification of discordant MDR /efflux+ and MDR1+/ef", Blood 86, 2329-2342.
  • Legrand, O., Simonin, G., Perrot, J.Y., Ziltoun, R. and Marie, J.P. (1998) "Pgp and MRP activities using calcein-AM are prognostic factors in adult acute myeloid leukemia patients", Blood 91, 4480-4488.
  • Legrand, O., Simonin, G., Beauchamp-Nicoud, A., Zittoun, R. and Marie. J.P (1999) "Simultaneous activity of MRP1 and Pgp is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia", Blood 94, 1046-1056.
  • Schneider, E., Cowan, K.H., Bader, H., Toomey, S., Schwartz, G.N., Karp, J.E. Burke, P.J. and Kaufmann, S.H. (1995) "Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia", Blood 85, 186-193.
  • Hart, S.M., Ganeshaguru, K., Scheper, R.J., Prentice, H.G., Hoffbrand, A. V. and Mehta, A.B. (1997) "Expression of the human major vault protein LRP in acute myeloid leukemia", Exp. Hemalol. 25, 1227-1232.
  • Heuvel-Eibrink, M.M., Wiemcr, E.A.C., Prins, A., Vossebeld, P., Meijerink, J., van der Holt, R., Pieters, R. and Sonneveld, P (2001) "Increased expression of the novel drug resistance gene BCRP, but not of MDRI. LRP/MVP. and MRP1 in relapsed/refractory AMI. using real time quantitative RT-PCR (Taqman analysis)", Leukemia 15, 487
  • Kuss, B.J., Deeley, R.G., Cole. S.P., Willman, C.L., Kopecky, K.J., Wolman, S.R., Eyre, H.J., Lane, S.A., Nancarrow, J. K. and Whitmore, S.A. (1994) "Deletion of gene for multidrug resistance in acute myeloid leukaemia with inversion in chromosome 16: prognostic implications", Lancet 343, 1531-1534.
  • Schiffer, C.A., Lee, E.J. Tomiyasu. T., Wiemik, P.H. and Testa. J.R. (1989) "Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia", Blood 73, 263-270.
  • Liu, P., Tarle, S.A., Hajra, A., Claxton, D.F., Marlton, P., Freedman, M., Siciliano, M.J and Collins, F.S (1993) "Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia", Science 261, 1041-1044.
  • Dohner, K., Schtenk, R.F., van der Reijden, B.A. and Donner, H. (2000) "Deletion of the multidrug resistance-associated protein (MRP1) gene in acute myeloid leukemia with inversion of chromosome 16 has no prognostic impact", Leukemia 14, 1154.
  • Taniguchi, K., Wada, M. Kohno, K., Nakamtira, T., Kawabe, T., Kawakami, M., Kagolani, K., Okumura, K. Akiyama, S. and Kuwano, M. (1996) "A human canaliculur multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin resistant human cancer cell lines with decreased drug accumulation", Cancer Res. 56, 4124-4129.
  • Kool, M., de Haas, M., Scheffer, G.L., Scheper, R.J., van Eijk, M.J. Juijn, J.A., Baas, F. and Borst. P. (1997) "Analysis of expression of cMOAT (MRP2) MRP3. MRP4. and MRP5. homologues of the multidrug resistance-associated protein gene (MRP1). in human cancer cell lines", Cancer Res. 57, 3537-3547.
  • Kool, M., van der Linden, M., de Haas, M., Baas, F. and Borst, P. (1999) "Expression of human MRP6. a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells", Cancer Res. 59, 175-182.
  • Hopper, E., Belinsky, M.G. Zeng, H., Tosolini. A., Testa, J.R. and Kruh. G.D. (2001) "Analysis of the structure and expression pattern of MRP7 (ABCC10). a new member of the MRP subfamily", Cancer Lett. 162, 181-191.
  • Lee, K., Belinsky, M.G., Bell, D.W., Testa, J.R. and Kruh, G.D. (1998) "Isolation of MOAT-B. a widely expressed mullidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter", Cancer Res. 58, 2741-2747.
  • Konig, J., Rost, D., Cui, Y. and Keppler, D (1999) "Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane", Hepatology 29, 1156-1163.
  • Paulusma, C.C., Kool, M., Bosma, P.J., Scheffer, G.L., ter Borg, F. Scheper, R.J., Tytgat, G.N., Borst, P., Baas, F. and Oude Elferink, R.P. (1997) "A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin Johnson syndrome", Hepatology 25, 1539-1542.
  • Kool, M., van der. L.M., de Haas, M., Scheffer, G.L., de Vree. J.M., Smith, A.J., Jansen, G., Peters, G.J., Ponne, N., Scheper, R.J., Elferink, R.P., Baas, F. and Borst, P. (1999) "MRP3. an organic anion transporter able to transport anti-cancer drugs", Proc. Natl Acad. Sci. USA 96, 6914-6919.
  • Wijnholds, J., Mol, C.A., van Deemter, L., de Haas, M., Scheffer, G.L., Baas, F., Beijnen, J.H., Scheper, R.J., Hatse, S., De Clercq, F., Balzarini, J. and Borsf, P. (2000) "Multidrug-resistance protein 5 is a multispeciftc organic anion transporter able to transport nucleotide analogs", Proc. Natl Acad Sci. USA 97, 7476-7481.
  • Madon, J., Hagenbuch, B., Landmann, L., Meier, P.J. and Stieger, B. (2000) "Transport function and hepatocellular localization of mrp6 in rat liver", Mol. Pharmacol. 57, 634-636.
  • Buchler, M., Konig, J., Brom, M., Kartenbeck, J., Spring, H., Horic, T. and Keppler, D. (1996) "cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein. cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats", J. Biol. Chem. 271, 15091-15098.
  • Paulusma, C.C., Bosma, P.J., Zaman, G.J., Bakker, C.T. Otter, M., Scheffe, G.L., Scheper, R.J., Borst, P. and Oude Elferink, R.P. (1996) "Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene", Science 271, 1126-1128.
  • Scheffer, G.L., Kool, M., Heijn, M., de Haas, M., Pijnenborg, A.C., Wijnholds, J., van Helvoort, A., de Jong, MC. Hooijberg, J.H., Mol, C.A., van der Linden, M., de Vree, J.M., van der Valk, K, Elferink, R.P., Borst, P. and Scheper, R.J. (2000) "Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies", Cancer Res. 60, 5269-5277
  • Ito, K., Suzuki, H., Hirohashi, T., Kume, K., Shimizu, T. and Sugiyama, Y. (1997) "Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR", Am. J. I'hysiol. 272, GI6-G22.
  • Suzuki, H. and Sugiyama, Y. (1998) "Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2", Semin. Liver Dis. 18, 359-376.
  • Hooijberg, J.H., Broxterman, H.J., Kool, M., Assaraf, Y.G., Peters, G.J., Noordhuis, P., Scheper. R.J., Borst, P., Pinedo, H.M. and Jansen, G. (1999) "Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2", Cancer Res. 59, 2532-2535.
  • Koike, K., Kawabe, T., Tanaka, T., Toh, S., Uchiumi, T., Wada, M., Akiyama, S., Ono, M. and Kuwano, M. (1997) "A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells", Cancer Res. 57, 5475-5479.
  • Cui, Y., Konig, J., Buchholz, J.K., Spring, H., Leier, J. and Keppler, D. (1999) "Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2. permanently expressed in human and canine cells", Mol. Phannacol, 55, 929-937.
  • Konig, J., Nies, A.T., Cui, Y., Leier, I. and Keppler, D. (1999) "Conjugale export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance", Biochim. Biaphys. Acta 1461, 377-394.
  • Stockel, B., Konig, J., Nies, A.T., Cui, Y. Brom, M. and Keppler, D. (2000) "Characterization of the S-flanking region of the human multidrug resistance protein 2 (MRP2) gene and its regulation in comparison with the multidrug resistance protein 3 (MRP3) gene", Eur. J. Biochem. 267, 1347-1358
  • Borst, P., Evers, R., Kool, M. and Wijnholds, J. (1999) "The multidrug resistance protein family", Biochim. Biophys. Acta 1461, 347-357.
  • Hirohashi, T., Suzuki, H. and Sugiyama, Y. (1999) "Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3)", J. Biol. Chem. 274, 15181-15185.
  • Young, L.C., Campling, B.G., Voskoglou-Nomikos, T., Cole, S.P., Deeley, R.G. and Gerlach, J.H. (1999) "Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response", Clin. Cancer Res. 5, 673-680.
  • Schuetz, J.D., Connelly, M.C., Sun, D., Paibir, S.G., Flynn, P.M., Srinivas, R.V., Kumar, A. and Fridland, A. (1999) "MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs", Nat. Med 5, 1048-1051.
  • Lee, K., Klein-Szanto, A.J. and Kruh, G.D. (2000) "Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells", J. Natl Cancer Inst. 92, 1934-1940.
  • Chen, Z.S., Lee, K. and Kruh, G.D. (2001) "Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine", J. Biol. Chem. 276, 33747-33754.
  • Jedlitschky, G., Burchell, B. and Keppler, D. (2000) "The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides", J. Biol. Chem. 275 30069-30074.
  • Der Kolk, D.M., Vellenga, F., Der Veen, A.Y., Noordhoek, L., Timmer-Bosscha, H., Ossenkoppele, G.J., Raymakers, R.A., Muller, M., van Den, B.E. and de Vries, E.G. (2000) "Deletion of the multidrug resistance protein MRP1 gene in acute myeloid leukemia: the impact on MRP activity", Blood 95, 3514-3519.
  • Chen, Y.N., Mickley, L.A., Schwartz, A.M., Acton, E.M., Hwang, J.L. and Fojo, A.T. (1990) "Characterization of adriamycinresistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein", J. Biol. Chem. 265, 10073-10080.
  • Lee, J.S., Scala, L., Matsumoto, Y., Dickstein, B., Robey, R., Zhan, Z., Altenberg, G. and Bates, S.E. (1997) "Reduced drug accumulation and multidrug resistance in human breast cancer cells without associated P-glycoproten or MRP overexpression", J. Cell Biochem. 65, 513-526.
  • Doyle, L.,Y. Ross, D.D., Sridhara, R., Fojo, A.T., Kaufmann. S.H., Lee, E.J. and Schiffer, C.A. (1995) "Expression of a 95-kDa membrane protein is associated with low daunorubicin accumulation in leukaemic blast cells", Br. J Cancer 71, 52-58.
  • Allikmets, R., Schriml, L.M., Hutchinson, A., Romano-Spica, V. and Dean, M. (1998) "A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance", Cancer Res. 58, 5337-5339.
  • Miyake, K., Mickley, L., Litman, T., Zhan, Z., Rohey, R. Cristensen, B., Brangi, M., Greenberger, L., Dean, M., Fojo, T. and Bates, S.E. (1999) "Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes", Cancer Res. 59, 8-13.
  • Cruop, J.M., Tiller, G.E., Fletcher, J.A., Lux, M.L., Raub, E., Goldenson, D., Son, D., Arciniegas, S. and Wu, R.L. (1997) "Isolation and characterization of a mammalian homolog of the Drosophila white gene", Gene 185, 77-85
  • Korualani, H., Kofani, H., Hara, Y. Nakagawa, R., Matsuinoto, M., Arakawa, H. and Nishimura, S. (2001) "Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specilic ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure", Cancer Res. 61, 2827-2832.
  • Honjo, Y. Hrycyna, CA., Yan, Q.W., Medina-Pérez. W.Y., Robey. R.W., van de Laar, A., Litman, T. Dean, M. and Bates, S.E. "Aquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in the MXR/BCRP/ABCP-overexpressing cells", Cancer Res. 2001; 61:6635-6639.
  • Maliepaard, M., Scheffer, G.L., Faneyte, I.E. van Gastelen, M.A., Pijnenborg, A.C., Schinkel, A.H., van De Vijver, M.J, Scheper, R.J. and Schellens, J.H. (2001) "Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues", Cancer Res. 61, 3458-3464.
  • Scheffer, G.L., Maliepaard, M., Pijnenborg, A.C., van Gastelen. M.A., de Jong, M.C., Schroeijers, A.B., van der Kolk, D.M., Allen, J.D., Ross, D.D., van der Valk, P., Dallon, W.S., Schellens, J.H. and Scheper, R.J. (2000) "Breast cancer resistance protein is localized at the plusma membrane in mitoxantrone- and topotecan-resistant cell lines", Cancer Res. 60, 2589-2593.
  • Rocchi, E., Khodjakov, A., Volk, F. L., Yang, C.H., Litruan, T., Bates, S.E. and Schneider, E. (2000) "The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane", Biochem. Biophys. Res. Commun. 271, 42-46.
  • Rabindran, S.K., He, H., Singh, M., Brown, E. Collins, K.I., Annable, T. and Greenberger, L.M. (1998) "Reversal of a novel multidrug resistance mechanism in human colon carcinoma cells by fumitremorgin C", Cancer Res. 58, 5850-5858.
  • de Bruin, M., Miyake, K., Litman, T., Robey, R. and Bales, S.E. (1999) "Reversal of resistance by GF120918 in cell lines expressing the ABC hall-transporter MXR", Cancer Lett. 146, 117-126.
  • Ross, D.D., Yang, W., Abruzzo, L.V., Dalton, W.S., Schneider, E., Lage, H., Diete, L.M., Greenberger, L., Cole. S.P. and Doyle, L.A. (1999) "Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxanlrone-selecied cell lines", J. Natl Cancer Inst. 91, 429-433.
  • Taylor, C.W., Dalton, W.S., Punish, P.R., Gleason, M.C., Bellamy, W.T. Thompson, F.H., Roe, D.J. and Trent, J.M. (1991) "Different mechanisms of decreased drug accumulation in doxorubicin and mitoxantrone resistant variants of the MCW human breast cancer cell Line", Br. J. Cancer 63, 923-929.
  • Lee, Y.J., Galoforo, S.S., Berns, C.M., Tong, W.P., Kim, H.R. and Corry, P.M. (1997) "Glucose deprivation-induced cytotoxicity in drug resistant human breast carcinoma MCF-7/ADR cells: role of c-myc and bcl-2 in apoptotic cell death", J. Cell Sci. 110(Pt 5), 681-686.
  • Maliepaard, M., van Gastelen, M.A., de Jong. L.A., Pluim, D., van Waardenburg, R.C. Ruevekamp-Helmers, M.C., Floot, B.C. and Schellens, J.H. (1999) "Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selccted ovarian tumor cell line", Cancer Res 59, 4559-4563.
  • Litman, T. Brangi, M., Hudson, E., Felsch, P. Abali, A., Ross. D.D., Miyake, K., Resuu, J.H. and Bates, S.E. (2000) "The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter MXR (ABCG2)", J. Cell Sci. 113(Pt 11), 2011-2021.
  • Ross, D.D., Karp, J.E., Chen, T.T. and Doyle, L.A. (2000) "Expression of breast cancer resistance protein in blast cells from patients with acute leukemia", Blood 96, 365-368.
  • van der Kolk, D.M., Vellenga, E., Scheffer, G.L., Muller, M., Bales, S.E., Scheper, R.J and de Vries, E.G.E. (2001) "Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia", Blood. ASH Abstr.
  • Hendricks, C.B., Rowinsky, E.K., Grochow, L.B., Donehower, R.C. and Kaufmann, S.H. (1992) "Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864). a new camptothecin analogue", Cancer Res. 52, 2268-2278.
  • Mankhetkom, S., Dubru, F. Hesschenbrouck, J., Fiallo, M. and Garnier-Suillerot. A. (1996) "Relation among the resistance factor, kinetics of uptake, and kinetics of the P-glycoprouin-mediated efflux of doxorubicin, daunorubicin. 8-(S)-fluoroidarubicin, and idarubicin in multidrug-resistant K562 cells", Mol. Pharmacol. 49, 532-539.
  • Zhou, D.C., Simonin, G., Faussai, A.M.,Zittoun, R. and Marie, J.P. (1997) "Effect of the multidrug inhibitor GG918 on drug sensitivity of human leukemic cells", Leukemia 11, 1516-1522.
  • Saito, T., Zhang, Z., Tokuriki, M., Ohtsubo, T., Shibamori, Y., Yamamoto, T. and Saito, H. (2001) "Cyclosporin A inhibits the extrusion pump function of P-glycoprotein in the inner ear of mice treated with vinblastine and doxorubicin", Brain Res. 901, 265-270.
  • Consoli, U., Van, N.T., Neamati, N., Mahadevia, R., Beran, M., Zhao, S. and Andrceff, M. (1997) "Cellular pharmacology of mitoxantrone in P-glycoprotein-positive and -negative human myeloid leukemic cell lines", Leukemia 11, 2066-2074.
  • Ushigome, F. Takanaga, H., Matsuo, H., Yanai, S., Tsukimori, K., Nakano, H., Uchiumi, T., Nakamura, T., Kuwano, M., Ohlani, H. and Sawada Y. (2000) "Human placental transport of vinblasline. vincrisline, digoxin and progesterone: contribution of P-glycoprotein", Eur. J. Pharmacol. 408, 1-10.
  • Malingre, M.M., Beijnen, J.H., Rosing, H., Koopman, F.J., Jewell. R.C., Paul, E.M., Bokkel Huinink, W.W. and Schellens, J.H. (2001) "Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients", Br. J. Cancer 84, 42-47.
  • Bardelmeijer, H.A., Beijnen, J.H., Brouwer, K.R., Rosing. H., Nooijen, W.J., Schellens, J.H. and van Tellingen, O. (2000) "Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein", Clin. Cancer Res. 6, 4416-4421.
  • Vanhoefer, U., Muller M.R., Hilger, R.A., Lindiner, B., Klaassen, U., Schleucher, N., Rustum, Y.M., Seeber, S. and Harstrick, A. (1999) "Reversal of MDR1-associated resistance to topotecan by PAK-200S. a new dihydropyridine analogue, in human cancer cell lines", Br. J. Cancer 81, 1304-1310.
  • Hoki, Y. Fujimori, A. and Pommier, Y. (1997) "Differential cytotoxicity of clinically important camptothecin derivatives in P-glycoprotein-overexpressing cell lines", Cancer Chemother. Phannacol, 40, 433-438.
  • Lorico, A., Rappa, G., Flavell, R.A. and Sartorelli, A.C. (1996) "Double knockout of the MRP gene leads to increased drug sensitivity in vitro", Cancer Res. 56, 5351-5355.
  • Young, L.C., Campling, B.G., Cole, S.P., Deeley, R.G and Gerlach, J.H. (2001) "Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer: correlation of protein levels with drug response and messenger RNA levels", Clin. Cancer Res. 7, 1798-1804.
  • Schneider, E., Horton, J.K., Yang, C.H., Nakagawa, M. and Cowan, K.H. (1994) "Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase 11 in a human breast carcinoma MCF7 cell line selected for etoposide resistance", Cancer Res. 54, 152-158.
  • Lee, D.W., Deeley, R.G. and Cole, S.P. (1998) "Characterization of vincristine transport by the M(r) 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione", Cancer Res. 58, 5130-5136.
  • Chen, ZS., Furukawa, T., Sumizawa, T., Ono, K., Ueda, K., Seto, K. and Akiyama, S.I. (1999) "ATP-dependent efflux of CPT-II and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P", MoI. Pharmacol. 55, 921-928.
  • Chu, X. Y., Suzuki, H., Ueda, K., Kalo, Y., Akiyama, S. and Sugiyama. Y. (1999) "Active efflux of CPT- II and its metabolites in human KB-derived cell lines", J. Phamacol. Exp. Ther. 288, 735-741.
  • Evers, R., Kool, M., van Deemter, L., Janssen, H., Calafal, J., Oomen, L.C., Paulusma, C.C., Gude Elferink, R.P., Baas, F, Schinkel, A.M. and Borst, P. (1998) "Drug export activity of the human canalicular multispecinc organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA", J. Clin. Invest. 101, 1310-1319.
  • Zeng, H., Bain, L.J., Belinsky, M.G. and Kruh, G.U. (1999) "Expression of multidrug resistance protein-3 (multispecific organic anion tiansporter-D) in human embryonic kidney 293 cells confers resistance to anticancer agents", Cancer Res. 59, 5964-5967.
  • Robey, R.W., Medina-Perez, W.Y., Nishiyaina, K., Lahusen, T., Miyake, K., Litman, T., Senderowicz, A.M., Ross, D.D. and Bates. S.E. (2001) 'Overexpression of the ATP-binding cassette half-transporter ABCG2 (Mxr/BCrp/ABCP1), in flavopyridol-resistant human breast cancer cells". Clin. Cancer Res. 7, 145-152.
  • Erlichman, C., Boerner, S.A., Hallgren, C.G., Spieker, R., Wang. X.Y., James, C.D., Scheffer, G.L., Maliepaard, M., Ross, D.D., Bible, K.C. and Kaufmann, S.H. (2001) "The HER tyrosine kinase inhibitor CH033 enhances cytotoxicity of 7-ethyl-10-hydroxy-camptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux", Cancer Res. 61, 739-748.
  • Maliepaard, M., van Gastelen, M.A., Tohgo, A., Hausheer, F.H., van Waardenburg, R.C., de Jong, L.A., Pluim, D., Beijnen, J.H. and Schellens, J.H. (2001) "Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918", Clin. Cancer Res. 7, 935-941.
  • Renes, R., de Vries, E.G.E., Jansen, P.L.M. and Muller, M.R. (2000) "The (patho)physiological functions of the MRP family", Drug Resist. Updates 3, 287-300.

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