摘要
目的 研究化疗药物诱导白血病细胞凋亡的作用及其与Bcl 2表达、临床预后指标及临床疗效的关系。方法 利用形态学观察、DNA琼脂糖凝胶电泳、凋亡指示抗体APO 2 .7结合流式细胞仪检测法 ,研究临床治疗相关剂量的化疗药物诱导急性淋巴细胞白血病 (ALL)细胞、急性混合性白血病 (HAL)细胞的凋亡及其Bcl 2表达率。结果 (1)用临床治疗相关剂量的长春新碱 (VCR)、地塞米松(Dex)、柔红霉素 (DNR)、阿糖胞苷 (Ara C)作用 2 0～ 2 4h后 ,多数患儿 (分别为 2 2 /2 4、19/2 4、6 /11、6 /6 )的白血病细胞可发生凋亡。但是DNR引起部分患儿 (3/11)的白血病细胞发生坏死。 (2 )VCR组与Dex组以及Ara C组与Dex组的诱导凋亡率呈高度正相关 ,相关系数分别为 0 .82 1(P <0 .0 0 1)和 0 .994(P <0 .0 0 1)。 (3)新鲜离体白血病细胞的凋亡率为 (3.2± 1.9) %。ALL及HAL细胞体外培养 2 4h后的自发凋亡为 (18.2± 13.5 ) % ,且与VCR ,Dex及Ara C的诱导凋亡率呈正相关 ,相关系数分别为 0 .878(P <0 .0 0 1)、0 .893(P <0 .0 0 1)、0 .882 (P <0 .0 5 )。 (4)CD3 4是影响白血病细胞凋亡率的独立指标。阳性组 (CD3 4≥ 30 % )的VCR、Dex诱导凋亡率及自发凋亡率明显低于阴性组。 (5 )白血病细胞的Bcl
Objective To study the ability of the chemotherapeutic drugs for inducing apoptosis and its relation to the Bcl 2 expression of leukemic cells, the prognostic factors and the efficacy of clinical treatment. Methods The morphologic study, agarose gel electrophoresis and flow cytometry were utilized to investigate the apoptosis of acute lymphoid leukemia (ALL) and hemoblastocy acute leukmia (HAL) cells induced by vincristine (VCR), dexamethasone (Dex), cytosine arabinoside (Ara C) and daunorubicin (DNR) at clinically relevant dosage. The flow cytometry was also used to study the expression of Bcl 2 on leukemic cells.Results (1) Exposure of leukemic cells to clinically relevant concentrations of VCR, Dex, Ara C and DNR for 20～24 hours resulted in apoptosis in most patients (22/24, 19/24, 6/11 and 6/6, respectively). Necrosis was found in leukemic cells of some patients (3/11) on DNR treatment. (2)The proportion of apoptotic cells induced by some chemotherapeutic drugs showed positive correlations with each other. The correlation coefficient of apoptotic rate in VCR group and Dex group was 0.821 ( P <0.001), in Ara C group and Dex group was 0.994 ( P <0.001). (3)The apoptotic rate of fresh leukemic cells was (3.2±1.9)%. ALL and HAL cells cultured for 24 hours in vitro would develop spontaneous apoptosis in (18.2±13.5)%. The spontaneous apoptosis rate correlated positively to the apoptosis rates induced by VCR, Dex and Ara c, the relevant coefficients were 0.878 ( P <0.001), 0.893 ( P <0.001) and 0.882 ( P <0.05), respectively. (4)CD 34 was an independent factor influencing apoptotic rates, the apoptotic rate was significantly lower in CD 34 positive group (CD 34 ≥30%) than that in CD 34 negative group. (5)There was no relationship between the expression of Bcl 2 and the apoptic rate of leukemic cells. Conclusion Inducing apoptosis is an important mechanism of killing leukemic cells by chemotherapeutic drugs.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2000年第4期223-227,共5页
Chinese Journal of Pediatrics
