Overexpression of multidrug resistance-associated p170-glycoprotein in acute non-lymphocytic leukemia

M. Michieli, D. Damiani, A. Geromin, A. Michelutti, R. Fanin, D. Raspadori, D. Russo, G. Visani, A. Dinota, S. Pileri, T. Tsuruo, M. Grandi, M. Baccarani, S. Tura

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Resistance to several cytotoxic agents, including anthracyclines, vinca alkaloids and epipodophylline derivatives (multidrug resistance, or MDR) can develop in tumor cells by overexpression of a 170-kd glycoprotein (p 170) which is an essential component of a membrane transport system leading to increased drug efflux and decreased intracellular drug concentration. By means of a p170-directed monoclonal antibody (MRK-16) and immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase technique), we investigated the expression of p170 in marrow blast cells of 59 cases (38 at diagnosis and 21 in relapse) of acute-non-lymphocytic leukemia (ANLL). The proportion of strongly MDR-positive cells was higher in relapse than at diagnosis (median 15.5% vs 1.5%). Out of 31 patients who were evaluable for the results of first remission induction, failure of first-line treatment (including Daunorubicin, standard-dose and high-dose Arabinosyl Cytosine, and sometimes also Mitoxantrone) occurred in 8/22 MDR-positive cases and in 1/9 MDR-negative ones (p = 0.21). Failure of first-line treatment was always associated with a progressive increase of p 170 expression. Total failures (no remission plus early relapse) were more frequent (p = 0.001) among MDR-positive cases (16/22) than among the others (2/9). These data show that MDR is very frequent in ANLL also at diagnosis and suggest that MDR can contribute to early failure of standard treatment.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalEuropean Journal of Haematology
Issue number2
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Hematology


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