Multidrug Resistance in Leukaemia

The treatment of many haematological malignancies is complicated by the development of resistance to cytotoxic agents. Cells which acquire the multidrug resistant (MDR) phenotype lose sensitivity to a spectrum of structurally unrelated chemotherapeutic drugs. Several distinct drug resistance mechanisms are now recognised which may be involved in clinically resistant leukaemia. It is possible that leukaemic cells may utilise one or more of these resistance processes as a survival mechanism and to maintain a proliferative advantage. If relevance of resistance mechanisms can be established, then the potential therapeutic benefit by circumvention of MDR is considerable with patients rendered chemosensitive and curable. There are many drugs which in vitro can reverse resistance processes, but their efficacy in vivo is yet to be fully demonstrated. It is likely that the final picture of the involvement of drug resistance in leukaemia will be complicated. Further investigation is warranted as the potential rewards are high.