Guerci A, Merlin J L, Missoum N, Feldmann L, Marchal S, Witz F, Rose C, Guerci O
Service de Médecine A. CHU Brabois, Vandoeuvre-lès-Nancy, France.
Blood. 1995 Apr 15;85(8):2147-53.
To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.
为评估多药耐药（MDR）表型的临床相关性，对87例成年急性白血病患者的细胞内柔红霉素蓄积（IDA）和P-糖蛋白（P-gp）表达进行了研究：69例初发急性髓系白血病（AML）患者、10例复发AML患者和8例继发于骨髓增生异常综合征的白血病（MDS-AML）患者。通过双标记流式细胞术分析确定IDA和P-gp表达。87例患者中，36例表达P-gp（41%）。与初发AML相比，复发AML和MDS-AML中P-gp表达更常见（P = .0001）。P-gp表达与CD34表达（P = .0003）和7号染色体异常（P = .027）显著相关。与P-gp阴性患者相比，P-gp阳性患者的IDA显著降低（P = .0007）。87例患者中，51例达到完全缓解（CR）。与CR患者相比，未缓解患者的IDA降低（22%±17%对42%±21%；P = 10⁻⁴）。36例P-gp阳性患者中有12例达到CR，而51例P-gp阴性患者中有40例达到CR（33%对78%；P = 10⁻⁴）。多因素分析证实了IDA和P-gp表达的预后价值。这些数据表明，测定IDA和P-gp表达可能有助于为AML患者设计治疗方案。
