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 Printable version |
Drug resistance in acute myeloid leukemias |
Hématologie. Volume 2, Number 5, 417-25, Septembre - Octobre 1996, REVUES ET MINI-REVUES
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 Résumé
Article gratuit
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Author(s) : Francis Lacombe, Francis Belloc, Jean-François Viallard, Christophe Grosset, Philippe Bernard, Josy Reiffers |
Summary : Many test for predicting the response of tumours to cytotoxic drugs have been developed in recent years. Since it is easy to obtain a suspension of viable cells, these test have been mainly applied to acute leukemia (AL). Here, we review their use in acute myeloid leukemia (AML). They may be divided into global functional tests, and biochemical and cytokinetic tests. The functional tests comprises the DiSC (differential staining Cytotoxicity), the MTT reduction, the FMCA (fluorometric microculture cytotoxicity assay) and clonogenic assays. The latter allows the chemosensitivity study of leukemic progenitors but is more time-consuming than the other three. They have all been correlated with treatment outcome. The biochemical and cytokenetic tests are based on the specific response of the leukemic cells to antineoplastic agent (i.e. mainly Ara-C and anthracylines). Proliferative activity (i.e. S phase percentage) and the rate of DNA synthesis measured by flow cytometry (FCM) before and after incubation of the leukemic cells with Ara-C is well correlated with treatment outcome. The influence of the expression of GP-170 (mdr1-related resistance) on treatment outcome has been widely studied but is still controversial, depending on the disease stage and the method used for its detection. Other resistance mechanisms have been described : overexpression of the mrp gene (multidrug resistance-associated protein), decreased levels of topoisomerase IIalpha, increased levels of glutathion-S-transferase Pi. The level of leukemic cell apoptosis induced by chemotherapy also seems to be related to chemoresistance. It is obvious that drug resistance is not monofactorial and that new drug resistance tests are required. They need further standardized evaluation in order to be included in a general therapeutic strategy and to help in improving the prediction of the resistance to treatment. |
Keywords : chemiosensitivity, acute leukemia. |
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