Screening for multidrug resistance in leukemia: cell reactivity to MRK-16 correlates with anthracycline retention and sensitivity of leukemic cells.
The biologic and clinical importance of the multidrug resistance (MDR) that is related with the overexpression of the P170 glycoprotein (Pgp) is widely recognized. However, a major issue that has not yet been solved is the definition of the degree of Pgp expression which is associated with a significant decrease of the sensitivity of the cells to chemotherapy. For this reason we studied the leukemic cells from 83 cases of acute leukemia. Leukemic cells were fixed in PLP and treated with saponine. Pgp expression was assayed by flow cytometry, using the anti Pgp monoclonal antibody MRK-16. Results were expressed both as the number of positive cells and by the intensity of the reaction as defined by the mean fluorescence index (MFI), i.e. the ratio between the mean fluorescence intensity of the MRK-16 incubated cells and of the IgG2a incubated cells. Thus, Pgp expression was compared with the results of two in vitro tests of cell sensitivity to anthracyclines, daunorubicin (DNR) cell retention and DNR cytotoxicity. We found that it was not the number of MRK-16 positive cells, but the degree of the reaction with MRK-16 (MFI) that significantly related to the anthracycline toxicity tests. Therefore, we propose that for clinical purposes a quick and cheap determination of Pgp-related MDR in leukemic cells may be obtained by measuring the MFI with MRK-16 in a standard flow cytometry assay and that the assay may indeed be sufficient to estimate Pgp expression as well as the influence of Pgp on cell sensitivity to anthracyclines.
Michieli
M
M
Department of Clinical and Morphological Research, University Hospital, Udine, Italy.
Damiani
D
D
Michelutti
A
A
Grimaz
S
S
Geromin
A
A
Fanin
R
R
Russo
D
D
Masolini
P
P
Baccarani
M
M
D018943:Anthracyclines / Q000378:metabolism / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents