Expression of multidrug resistance-associated protein (MRP) and multidrug resistance (MDR1) genes in acute myeloid leukemia.
The frequency, prognostic value and interrelation of MRP and MDR1 gene expressions were investigated by quantitative reverse transcription polymerase chain reaction (RT-PCR) in 91 cases of de novo acute myeloid leukemia (AML), of which 51 were newly diagnosed, 21 were relapsed, and 19 were refractory patients. As compared with normal bone marrow cells and peripheral granulocytes, an overexpression of MRP gene was found in 24% (22 of 91) cases of de novo AML. The incidence of MRP gene overexpression tended to be higher in relapsed patients than in newly diagnosed patients (38 vs 18%, P = 0.063). In 52 evaluable newly diagnosed and relapsed patients treated with MDR-related drugs, both MRP and MDR1 gene overexpressions correlated to a higher rate of emergence of clinical drug resistance (83 vs 22%, P = 0.005; and 67 vs 24%, P = 0.045, respectively). A positive correlation was found between MRP and MDR1 gene overexpressions (R = 0.53, P < 0.001). Analysis of 46 evaluable MDR1-negative cases revealed a trend for higher resistant disease rate in MRP-positive patients as compared with MRP-negative patients (100 vs 20%, P = 0.053). These data suggest that MRP, like MDR1, may have an important negative impact on the outcome of chemotherapy, and that there may be a common mechanism of induction for the overexpression of these two genes.
Zhou
D C
DC
Laboratoire de Cinétique et de Cultures Cellulaires, Formation de Recherche Claude Bernard, Hôpital Hôtel-Dieu, Université Paris VI, France.
Zittoun
R
R
Marie
J P
JP
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins