Abstract
P-glycoproteins (Pgps) belong to the family of ATP binding cassette (ABC) transporter proteins. In humans two Pgp genes have been identified; mdr-1 and mdr-3. Classical Multiple Drug Resistance (MDR) is associated with over expression of the mdr-1 gene product, P-170. No role for mdr-3 in MDR has yet been proven. However there is evidence that mdr-3 overexpression may be associated with drug resistance in certain B-cell lymphocytic leukaemias. In an immunocytochemical study we have looked at a selection of B-cell leukaemias for mdr-1 and mdr-3 encoded Pgp expression using monoclonal antibodies specific for the mdr-1 and mdr-3 encoded gene products. In B-CLL patients a differential pattern of MDR-3 positive staining was observed; suggesting that MDR-3 positivity may be associated with a more malignant phenotype in B-CLL. This pattern was not observed with MDR-1 positivity. We also observed MDR-3 positivity in an AML stage M5a patient which is the first report of MDR-3 Pgp expression being detected in AML; suggesting that MDR-3 Pgp expression may be limited to particular subtypes of this disease.
Results from B-NHL cases were inconclusive with varying expression of MDR-1 and MDR-3 Pgps observed. Work is currently underway to further explain the significance of these findings.
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References
Schinkel AH, Roelofs MEM, Borst P. Characterisation of the human MDR-3 P-glycoprotein and its recognition by P-glycoprotein-specific monoclonal antibodies. Ca Res, 51(10), 2628–2635 (1991).
Roninson IB, Chin JE, Choi K et al.. Isolation of human mdr DNA sequences amplifed in multidrug resistant KB carcinomas cells. Proc. Natl. Acad. Sci. USA, 83, 4538 (1986).
Van Der Bliek AM, Baas F, Ten Houte-De-Lange T, Kooiman PM, Van Der Velde-Koerts T, Borst P. The human mdr-3 gene encodes a novel p-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver. EMBO J, 6, 3325 (1987).
Roninson IB. The role of mdr-1 (P-glycoprotein) gene in multidrug resistance in vitro and in vivo. Biochem Pharacol, 43, 95–102 (1992).
Clynes M. Cellular models for multidrug resistance in cancer. In Vitro Cell Dev Biol, 29A, 171–179 (1993).
Kino K, Taguchi Y, Yamada K, Komano T, Ueda K. Aureobasidin A an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR-1 and MDR-2/ P-glycoproteins. FEBS Lett, 399, 29–32 (1996).
Nooter K, Sonnevald P, Janssen A, Oostrum R, Boersma T, Herweijer H, Valerio D, Hagemeijer A, Baas F. Expression of the mdr-3 gene in prolymphocytic leukemia: association with cyclosporin-A induced increase in drug accumulation. Int J Ca., 45, 626–631 (1989).
Herweijer H, Sonneveld P, Baas F, Nooter K. Expression of mdr-1 and mdr-3 Multidrug-resistance Genes in Human Acute and Chronic Leukemias and association with stimulation of drug accumulation by cyclosporine. J Natl Ca Inst., 82(13), 1133–1140 (1990).
Arai Y, Masuda M, Sugawara I, Arai T, Motoji T, Tsuruo T, Oshimi K, Mizoguchi H. Expression of the MDR-1 and MDR-3 gene products in acute and chronic leukemias. Leuk Res, 21, 313–319 (1997).
Sonneveld P, Nooter K, Burghouts JTM, Herweijer H, Adriaansen HJ, van Dongen JJM. High Expression of the mdr-3 Multiple Resistance Gene in Advanced Stage Chronic Lymphocytic Leukemia. Blood, 79(6), 1496–1500 (1992).
Nooter K, Sonneveld P. Multidrug resistance (MDR) genes in haematological malignancies. Cytotechnology., 12, 213–230 (1993).
Ludescher C, Hilbe W, Eisterer W, Preuss E, Huber C, Gotwald M, Hofmann, Thaler J. Activity of P-glycoprotein in B-cell Chronic Lymphocytic leukaemia determined by a flow cytometric assay. J. Natl Cancer. Inst., 85(21), 1751–1758 (1993).
Marie JP, Zhou DC, Gurbuxani S, Legrand O, Zittoun R. Mdr-1/ P-glycoprotein in Haematological Neoplasms. Eur J Ca., 32A(6), 1034–1038 (1996).
Nussler V, Pelka-Fleischer R, Zwierzina H, Nerl C, Beckert B, Gieseler F, Diem H, Ledderose, Gullis E, Sauer H, Wilmanns W. P-glycoprotein expression in patients with acute leukemias — clinical relevance. Leukemia 10, Suppl 3, S23–S31 (1996).
Pileri SA, Sabattini, Falani B, Tazzari PL, Gherlinzoni F, Michieli MG, Damiani D, Zucchini L, Gobbi M, Tsuro T, Baccarani M. Immunohistochemical detection of the multidrug transport protein P170 in human normal tissues and malignant lymphomas. Histopathology, 19, 131–140 (1991).
Cheng A, Su I, Chen Y, Lee T, Wang C. Expression of p-glycoprotein and glutathione-S transferase in recurrent lymphomas: the possible role of Epstein-Barr virus, immunophenotypes, and other predisposing factors. J Clin Oncol, 11, 109–115 (1993).
Rodriguez C, Commes T, Robert J, Rossi J. Expression of p-glycoprotein and anionic glutathione s transferase genes in non-Hodgkins’s lymphoma. Leuk Res, 17, 149–156 (1993).
Niehans G, Jaszcz W, Brunetto V, et al. Immunohistochemical identification of p-glycoprotein in previously untreated, diffuse large cell and immunoblastic lymphomas. Ca Res, 52, 3668–3657 (1992).
Moran E, Larkin AM, Doherty G, Kelehan P, Kennedy SM, Clynes M. A new mdr-1 encoded P-170 specific monoclonal antibody: (6/1C) on paraffin wax embedded tissue without pre treatment of sections. J Clin Pathol., 50(6), 465–471 (1997).
Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques. J Histchem Cytochem., 29, 577–580 (1981).
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Larkin, A., Moran, E., Alexander, D., Clynes, M. (1999). Preliminary Immunocytochemical Studies of MDR-1 and MDR-3 Pgp Expression in B-Cell Leukaemias. In: Kaspers, G.J.L., Pieters, R., Veerman, A.J.P. (eds) Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol 457. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4811-9_8
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DOI: https://doi.org/10.1007/978-1-4615-4811-9_8
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