Molecular mechanisms of drug resistance in acute myeloid leukaemia.
Resistance to chemotherapy in acute myeloid leukaemia is a major obstacle to a successful outcome for many patients. Often, there is resistance against a broad range of drugs due to multiple, simultaneously active processes. These mechanisms include effects on drug influx and efflux, drug activation/inactivation, DNA repair mechanisms, altered response of end targets, an altered haematopoietic microenvironment and dysfunctional apoptotic pathways. This article reviews the factors that determine leukaemic cell chemosensitivity and discusses the potential for rationally guided therapy.
McLornan
Donal P
DP
Medical Research Council Clinical Research Fellow, Queen's University Belfast, Centre for Cancer Research and Cell Biology, BT7 1NN, Northern Ireland, UK.
McMullin
Mary Frances
MF
Johnston
Patrick
P
Longley
Daniel B
DB
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological
D000970:Antineoplastic Agents; D020169:Caspases