Multidrug resistance: clinical relevance in acute leukemia.
The multidrug resistance (MDR) phenotype represents an important major mechanism of resistance to anthracyclines and related natural products that lends itself to clinical exploitation. Overexpression of the mdr1 gene or its glycoprotein product has been linked to a number of poor prognostic factors in acute myeloid leukemia and adversely affects treatment outcome. Clinical trials are now under way testing pharmacologic modulators of MDR in acute leukemia. Although preliminary results are encouraging, MDR modulators may alter the clearance of some antineoplastics and thereby confound interpretation of randomized trials. This review examines diagnostic methods of MDR detection, its prevalence and impact in acute leukemia, and strategies for MDR reversal.
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Section of Hematology/Oncology, Arizona Cancer Center, Tucson.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification*; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins