Abstract
We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo acute myeloid leukemia (AML) at the initial diagnosis in order to further define the relationship between the presence of P-gp on leukemic cells and the efficacy of two different anthracycline drugs, Daunorubicin (DNR) and Idarubicin (IRR), in terms of remission, induction and survival. We found that 30 (60%) of the 50 patients were negative for P-gp expression (group 1) and 20 patients (40%) were positive (group 2) for P-gp expression by MRK16 MoAb using a cut of 10% positive cells. Among the 50 patients, 35 (70%) obtained complete remission (CR); depending on P-gp expression the CR rate was 80% for group 1 and 45% for group 2 (p<0.005). The median duration of overall survival (OS) was 20 months for patients in group 1, compared to 10 months for patients in group 2 (p<0.005). Regarding the anthracycline used, no difference in CR has been observed in patients of group 1 (75% CTR with DNR versus 90% CR with IDR); on the contrary in group 2 we observed 40% CR with DNR versus 70% CR with IDR (p<0.005). No significant difference has been achieved in group 1 terms of median duration ofoverall survival between DNR and IDR regimen; on the contrary the median duration of OS in patients of group 2 treated with IDR regimen was significantly longer than DNR regimen (p<0.005). These results confirm the prognostic value of P-gp expression in AML at diagnosis and we suggest that Idarubicin could be a valid anthracycline drug for reversing multidrug resistance.
Similar content being viewed by others
References
Arlin ZA, Case D, Moore J, Wiernik P, Felsman E, Salatan S, Desali P and the Lederle Cooperative Group (1990). Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia. Leukemia 4: 177.
Berman E, Heller G, Santorsa J, McKenzie S, Gee TS, Kempin S, Gulati S, Andreeff M, Kolitz J, Gabrilove J, Reich L, Mayer K, Keefe D, Trainor K, Schluger A, Penenberg D, Raymond V, O'Reilly R, Jhanwar S, Young C and Clarkson B (1991) Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adults patients with newly diagnosed acute myelogenous leukemia. Blood 77: 1666.
Berman E and McBride M (1992) Comparative Cellular Pharmacology of Daunorubicin and Idarubicin in Human Multidrug-Resistant Leukemia Cells. Blood; 79: 3267–3273.
Biedler J and Riehm H (1990) Cellular resistance to acitomycin D in Chinese hamster cellsin vitro. Cross resistance, radioaudiographic, and cytogenetic studies. Cancer Res 30: 1174.
Campos L, Guyotat D, Archimbaud E, Calmard-Oriol P, Tsuruo T, Troncy J, Treille D and Fiere D (1992) Clinical Significance of Multi drug Resistance P-Glycoprotein Expression on Acute Nonlymphoblastic Leukemia Cells at Disgnosis. Blood 79: 473–476.
Into T, Miyazaki H, Isogai M, Nomura T, Tsuzuki M, Tsuruo T, Ezaki K and Hirano K (1994) Expression of P-Glycoprotein inDe Novo Acute Myelogenous Leukemia in Initial Diagnosis: results of Molecular and Functional Assay, and correlation with Treatment Outcome. Leukemia 8: 1492–1497.
Kaplan EL and Meier P (1958) Non parametric estimation from incomplete observations. J Am Stat Assoc 53: 457–458.
Kartner N, Riordan JR and Ling V (1983) Cell surface P-glycoprotein is associate with multidrug resistance in mammalian cell lines. Science 221: 1285.
Kaya SB and Kerr DJ (1991) Multidrug Resistance: Clinical Relevance in Haematological Malignancies. Blood Reviews 5: 38–41.
Marie JP, Zittoun R and Sikic BI (1991) Multidrug resistance (mdr1) Gene Expression in Adult Acute leukemias: Correlations With Treatment Outcome and In Vitro Drug Sensitivity. Blood 78: 586–592.
Marie JP, Faussat-Suberville AM, Zhou D and Zittoun R (1993) Daunorubicin Uptake by Leukemic Cells: Correlations with Treatment Outcome andmdr1 Expression. Leukemia 7: 825–831.
Michieli M, Michelutti A, Damiani D, Pipan C, Raspadori D, Lauria F and Bassarani M (1993) A Comparative Analysis of the sensitivity of Multidrug Resistant (MDR) and Non-MDR Cells to Different Anthracycline Derivates. Leukemia and Lymphoma 9: 255–264.
Musto P, melilloL, Lombardi G, Matera S, Di Giorgio G and Carotenuto M (1991) High risk of early resistant relapse for leukaemic patients with presence of multidrug resistance associated P-glycoprotein positive cells in complete remission. British Journal of Haematology 77: 50–53.
Pastan I and Gottesman MM (1991) Multidrug Resistance. Annu Rev Med 42: 277–286.
Pirker R, Wallner J, Geissler K, Linkesch W, Haas OA, bettelheim P, Hopfner M, Scherrer R, Valent P, Havelec L, Ludwig H and Lechner K (1991) MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst 83: 708–712.
Pirker R, Eallner J, Götzl M, Gsur A, geissler K, Havelec L, Haas O, Linkesch W and Lechner K (1992) MDR1 RNA expression is an independent progostic factor in acute myeloid leukemia. Blood 80: 557–558.
Priesler H, Davis RB, Kirshner J, Dupre E, Richards F, Hoagland HC, Kopel S, Levy RN, Carey R, Schukman P, Gottlieb A, McIntyre OR and the Cancer and Leukemia Group B (1987) Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlynphocytic leukemia: A Cancer and Leukemia Group B study. Blood 69: 1441.
Sato H, Preisler H, Day R, Raza A, Larson R, Brownman G, Goldberg J, Vogler R, Grunwald H, Gottlieb A, Bennet J, Gottesman M and Pastan I (1990) MDR1 transcript levels as an indication of resistant disistant in acute myelogenous leukemia. Br J Ematol 75: 340–345.
Simon SM and Schindler M (1994) Cell biological mechanisms of multidrug resistance in tumors. Proc Natl Acad Sci USA 91: 3497–3504.
Slapak CA, Mizunuma N and Kufe DW (1994) Expression of the Multidrug Resistance Associated Protein and P-Glycoprotein in Doxorubicin-Selected Human Myeloid Leukemia cells. Blood 84: 3113–3121.
Tsuruo T, Sugimoto Y, Hamada H, Roninson I, Okumura M, Adachi K, Morishima Y and Ohno R (1987) Detection of multidrug resistance markers, P-glycoprotein and mdr1 mRNA, in human leukemia cells. Jpn J Cancer Res 78: 1415.
Weinstein HJ, Mayer RJ, Rosenthal DS, Camitta B, Coral FS, Nathan DH and Frei E (1980) Treatment of acute myelogenous leukemia in children and adults. N Engl J Med 303: 472.
Wood P, Burgess R, MacGregor A and Liu Yin JA (1994) P-glycoprotein expression on acute meyeloid leukemia blast cells at diagnosis predicts response to chemotherapy and survival. British Journal of Haematology 87: 509–514.
Zhou DC, Marie JP, Suberville A and Zittoun R (1992) Relevance of mdr1 gene expression in acute myeloid leukemia and comparison of different methods. Leukemia 6: 879–885.
Zöchbauer S, Gsur A, Brunner R, Kyrle PA, Lechner K and Pirker R (1994) P-Glycoprotein Expression ans Unfavorable Prognostic factor in Acute Myeloid Leukemia. Leukemia 8: 974–977.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pogliani, E.M., Belotti, D., Rivolta, G.F. et al. Anthracycline drugs and MDR expression in human leukemia. Cytotechnology 19, 229–235 (1996). https://doi.org/10.1007/BF00744217
Issue Date:
DOI: https://doi.org/10.1007/BF00744217