Senent L, Jarque I, Martín G, Sempere A, González-García Y, Gomis F, Pérez-Sirvent M, De La Rubia J, Sanz M A
Hematology Service, La Fe University Hospital, Valencia, Spain.
Haematologica. 1998 Sep;83(9):783-7.
Drug resistance has become a major cause of treatment failure in patients with acute leukemia. P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype, has been reported to be an important predictor of treatment outcome. The aim of this study was to analyze the value of Pgp expression in bone marrow or peripheral blood as a predictor of the response to remission induction chemotherapy as well as the duration of remission in patients with de novo acute myeloid leukemia (AML).
We examined the expression of Pgp in 82 patients with de novo AML using an immunocytochemical assay with the C219 monoclonal antibody.
Twenty-seven of the 82 patients (33%) were C219-positive in from 1% to 100% of their cells. Thirteen cases (16%) showed a positive reaction in more than 50% of the leukemic cells. Only hyperleukocytosis was significantly associated with higher expression of Pgp. Although 8 of the 13 cases (62%) with more than 50% of cells having Pgp expression were CD34-positive, this association was not statistically significant. A univariate analysis of resistance to induction therapy showed a significantly higher resistance rate in patients with increased Pgp expression (P = 0.01) as well as in those patients with decreased reactivity to myeloperoxidase. The multivariate analysis revealed the independent prognostic value of Pgp expression. C219 reactivity did not have an influence on remission duration.
Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.
耐药已成为急性白血病患者治疗失败的主要原因。据报道，与多药耐药（MDR）表型相关的P - 糖蛋白（Pgp）是治疗结果的重要预测指标。本研究旨在分析骨髓或外周血中Pgp表达作为初发急性髓系白血病（AML）患者缓解诱导化疗反应及缓解持续时间预测指标的价值。
我们使用C219单克隆抗体免疫细胞化学分析法检测了82例初发AML患者的Pgp表达。
82例患者中有27例（33%）其1%至100%的细胞C219呈阳性。13例（16%）白血病细胞中超过50%呈阳性反应。仅白细胞增多症与Pgp的高表达显著相关。虽然13例细胞中超过50%有Pgp表达的病例中有8例（62%）CD34呈阳性，但这种相关性无统计学意义。诱导治疗耐药的单因素分析显示，Pgp表达增加的患者（P = 0.01）以及髓过氧化物酶反应性降低的患者耐药率显著更高。多因素分析揭示了Pgp表达的独立预后价值。C219反应性对缓解持续时间无影响。
我们的数据表明，P - 糖蛋白表达是初发AML患者诱导治疗耐药的可靠标志物。
