Multidrug resistance in haematological malignancies.
The development of refractory disease in acute myeloid or lymphoblastic leukaemias (AML, ALL) and multiple myeloma (MM) is frequently associated with the expression of one or several multidrug resistance (MDR) genes. MDR1, MRP1 and LRP have been identified as important adverse prognostic factors in AML, T-ALL and MM. Recently, it has become possible to reverse clinical multidrug resistance by blocking P-glycoprotein-mediated drug efflux. The potential relevance of these reversal agents of MDR and potential new approaches to treat refractory disease are discussed.
Sonneveld
P
P
University Hospital Rotterdam - Dijkzigt, Department of Hematology, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. sonneveld@haed.azr.nL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003524:Cyclosporins / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003524:Cyclosporins; D004791:Enzyme Inhibitors