Wuchter C, Karawajew L, Ruppert V, Schrappe M, Harbott J, Ratei R, Dörken B, Ludwig W D
Department of Haematology, Oncology and Tumour Immunology, Robert-Rössle-Clinic, Charité, Humboldt-University of Berlin, Germany.
Br J Haematol. 2000 Jul;110(1):154-60. doi: 10.1046/j.1365-2141.2000.02147.x.
CD95 (Fas/APO-1) expression and function and Bcl-2 expression, as well as spontaneous apoptosis in vitro, have been shown to be predictive markers for the in vivo response to chemotherapy in acute myeloid leukaemia (AML). To determine the clinical significance of apoptosis-regulating factors in acute lymphoblastic leukaemia (ALL), we investigated cell samples of children with ALL who had been included in the German ALL Berlin-Frankfurt-Münster (BFM) study using flow cytometry for constitutive expression levels of CD95 (n = 110) and Bcl-2 (n = 110). Furthermore, we determined the extent of spontaneous apoptosis in vitro (n = 102) and susceptibility to anti-CD95-induced apoptosis (CD95-sensitivity) (n = 97). We correlated these findings with the functional activity of the multidrug resistance (MDR)-associated P-glycoprotein (P-gp), as detected by the rhodamine123 efflux test, immunophenotype, cytogenetics and clinical data of the patients examined. Good responders to initial prednisone therapy ('prednisone response') revealed significantly higher Bcl-2 expression levels [5.4 +/- 3.4 relative fluorescence intensity (RFI), n = 68] than poor responders (3.7 +/- 2.6 RFI, n = 42; P = 0.002). There was no significant correlation between the other investigated parameters and prednisone response. Moreover, neither the CD95 and Bcl-2 expression levels nor the extent of spontaneous apoptosis in vitro, CD95 sensitivity or P-gp function were correlated with the response to induction chemotherapy or relapse rate, either for B-cell precursor ALL or T-cell ALL. No consistent pattern of change in CD95 (n = 10) and Bcl-2 expression (n = 9) was noted in cases studied at both initial diagnosis and relapse. In conclusion, our findings underline the different cell biological features of primary AML and ALL cells.
CD95（Fas/APO-1）的表达与功能、Bcl-2的表达以及体外自发凋亡，已被证明是急性髓系白血病（AML）体内化疗反应的预测标志物。为了确定凋亡调节因子在急性淋巴细胞白血病（ALL）中的临床意义，我们对纳入德国ALL柏林-法兰克福-明斯特（BFM）研究的ALL患儿的细胞样本进行了研究，采用流式细胞术检测CD95（n = 110）和Bcl-2（n = 110）的组成性表达水平。此外，我们还测定了体外自发凋亡的程度（n = 102）以及抗CD95诱导凋亡的敏感性（CD95敏感性）（n = 97）。我们将这些结果与通过罗丹明123外排试验检测的多药耐药（MDR）相关P-糖蛋白（P-gp）的功能活性、免疫表型、细胞遗传学以及所检查患者的临床数据进行了关联分析。初始泼尼松治疗的良好反应者（“泼尼松反应”）显示Bcl-2表达水平显著高于反应不佳者[5.4±3.4相对荧光强度（RFI），n = 68]（3.7±2.6 RFI，n = 42；P = 0.002）。其他研究参数与泼尼松反应之间无显著相关性。此外，无论是B细胞前体ALL还是T细胞ALL，CD95和Bcl-2表达水平、体外自发凋亡程度、CD95敏感性或P-gp功能均与诱导化疗反应或复发率无关。在初诊和复发时研究的病例中，未观察到CD95（n = 10）和Bcl-2表达（n = 9）的一致变化模式。总之，我们的研究结果强调了原发性AML和ALL细胞不同的细胞生物学特征。
