Ong Y L, McMullin M F, Bailie K E, Lappin T R, Jones F G, Irvine A E
Haematology Research Laboratory, Queen's University of Belfast, Belfast City Hospital, UK.
Br J Haematol. 2000 Oct;111(1):182-9. doi: 10.1046/j.1365-2141.2000.02315.x.
Most cytotoxic drugs kill cells by instigating the process of apoptosis and it has been suggested that apoptotic markers may provide an indication of tumour chemosensitivity. The aim of this study was to determine if such a relationship exists in acute myeloid leukaemia (AML). The levels of spontaneous apoptosis, bcl-2 and bax were evaluated in 56 newly diagnosed AML patients to determine if they correlated with a response to cytotoxic therapy. Spontaneous apoptosis was lower, but bcl-2, bax and the bcl-2/bax ratio were higher in AML compared with normal individuals. AML patients with high bax expression at diagnosis had significantly better prognosis for disease-free survival, event-free survival and overall survival (P = 0.016). In the standard risk group, high bax expression was in keeping with significantly improved survival. Multivariate analysis revealed bax to be an independent predictor of survival. There was a significant reduction in bcl-2 and bax expression when AML patients entered complete remission and also in relapsed AML patients who entered a second remission. This study suggests that bax is a useful prognostic indicator in AML and may assist with therapeutic decision-making for patients in the standard risk category.
大多数细胞毒性药物通过引发细胞凋亡过程来杀死细胞,有人提出凋亡标志物可能提示肿瘤的化疗敏感性。本研究的目的是确定急性髓系白血病(AML)中是否存在这种关系。对56例新诊断的AML患者的自发凋亡水平、bcl-2和bax进行评估,以确定它们是否与细胞毒性治疗反应相关。与正常个体相比,AML患者的自发凋亡较低,但bcl-2、bax和bcl-2/bax比值较高。诊断时bax高表达的AML患者无病生存、无事件生存和总生存的预后明显更好(P = 0.016)。在标准风险组中,高bax表达与生存显著改善一致。多因素分析显示bax是生存的独立预测因素。AML患者进入完全缓解时以及复发的AML患者进入第二次缓解时,bcl-2和bax表达均显著降低。本研究表明,bax是AML中一个有用的预后指标,可能有助于标准风险类别患者的治疗决策。