Tóthová E, Elbertová A, Fricová M, Kafková A, Hlebasková M, Svorcová E, Stecová N, Guman T, Raffac S
Department of Hematology, Medical Faculty Hospital and UPJS, Kosice, Slovak Republic.
Neoplasma. 2001;48(5):393-7.
Drug resistance has become a major cause of the treatment failure in patients with acute leukemia. P-glycoprotein (P-gp), which is associated with multidrug resistance (MDR) phenotype, has been reported to be an important predictor of the treatment outcome. The aim of this study was to analyze the value of P-gp expression in bone marrow cells as a predictor of the response to remission induction chemotherapy, as well as duration of remission in adult patients with newly diagnosed acute myeloid leukemia (AML). We examined the expression of P-gp in 31 patients using the monoclonal antibody UIC2. Direct immunofluorescent labeling was performed and samples were analyzed by flow cytomery. Kolmogorov-Smirnov test (D-value) was used to estimate UIC2 staining. A D > or = 0.3 for labeling of gated leukaemic blasts as compared to that of the isotypic control was defined positive (+) and compared to clinical data. P-gp expression was found in 14/31 (45.6%) patients, 17/31 (54.8%) of the samples were found P-gp negative(-). No correlation was found regarding age, sex and FAB subtype, altough 6/14 (43%) cases with more than 50% of cells having P-gp expression, were CD34+/CD7+. Complete remission rates were significantly lower in UIC2+ patients than in UIC2- cases (70% vs 35%, p < 0.01). Complete remission duration was also shorter in UIC2+ patients (6 vs 12.4 months). Our data indicate, that P-gp expression is a reliable marker of resistance to induction treatment in patients with de novo AML and can help to identify patients who may require alternative regimens designed to overcome therapy resistance.
耐药性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（P-gp）是治疗结果的重要预测指标。本研究旨在分析骨髓细胞中P-gp表达作为新诊断的急性髓系白血病（AML）成年患者缓解诱导化疗反应及缓解持续时间预测指标的价值。我们使用单克隆抗体UIC2检测了31例患者P-gp的表达。进行直接免疫荧光标记，并通过流式细胞术分析样本。采用Kolmogorov-Smirnov检验（D值）评估UIC2染色。与同型对照相比，门控白血病母细胞标记的D值≥0.3定义为阳性（+），并与临床数据进行比较。14/31（45.6%）例患者检测到P-gp表达，17/31（54.8%）的样本P-gp呈阴性（-）。未发现年龄、性别和FAB亚型与之相关，尽管14例中有6例（43%）P-gp表达细胞超过50%的病例为CD34+/CD7+。UIC2阳性患者的完全缓解率显著低于UIC2阴性患者（70%对35%，p<0.01）。UIC2阳性患者的完全缓解持续时间也较短（6个月对12.4个月）。我们的数据表明，P-gp表达是初治AML患者诱导治疗耐药的可靠标志物，有助于识别可能需要替代方案以克服治疗耐药的患者。
