四硫化四砷治疗急性早幼粒细胞白血病过程中PML/PML-RARα蛋白的变化

Change of PML/PML-RARα Protein during Treatment with Tetraarsenic Tetrasulfide (As_4S_4) in Patients with Acute Promyelocytic Leukemia

为了研究四硫化四砷 (As4S4)对急性早幼粒细胞白血病 (APL)患者白血病细胞中PML/PML RARα蛋白的作用 ,在患者治疗前和治疗后不同时间多次留取骨髓或外周血标本 ,用抗PML蛋白单抗对APL细胞进行间接免疫荧光染色 ,并在荧光显微镜下观察荧光信号的演变规律。结果显示 :治疗前APL细胞表现为细胞核内弥漫分布的大量微颗粒荧光信号。As4S4 治疗后 ,最早于第 2天即可出现荧光分布的改变 ,表现为微荧光颗粒消失 ,出现数个大荧光颗粒 ,并出现核周荧光 ,最终大荧光颗粒也消失。当As4S4 合用全反式维甲酸 (ATRA)时 ,PML蛋白荧光信号变化规律与单用As4S4 基本相同。但单独应用ATRA治疗后 ,PML蛋白荧光信号的改变与前两组明显不同 ,主要差别为微荧光颗粒不会很快消失 ,而是在微荧光颗粒逐渐减少的基础上 ,出现越来越多的大荧光颗粒 ,最终微荧光颗粒消失 ,而大荧光颗粒始终存在。结论 :As4S4 使患者体内APL细胞的PML/PML RARα蛋白发生重新分布 。

In order to explored the change of PML/PML-RARα protein during tetraarsenic te trasulfide (As 4S 4) treatment, acute promyelocytic leukemia (APL) cells from a group of newly diagnosed APL patients were examined by indirect immunofluoresce nce staining with anit-PML monoclonal antibody. The results showed that all s amples typically presented many microspeckle signals throughout the nucleus before treatment. The redistribution occured as early as on the second d ay after As 4S 4 treatment, which revealed loss of microspeckles with the presentation of a few large speckles. Anti-PML staining also emerged in the peri nuclear cytoplasm. At last, microspeckles and large speckles all disappeared. W hen the tharepy was combining all-trans-retinoic acid (ATRA) with As 4S 4, similar results were obtained. However, APL cells from patients trea ted with ATRA alone performed totally different appearance, presenting microspe ckles and large speckles at the same time, followed with entirely large speckles . The co nclusion is that As 4S 4 makes redistribution of PML/PML-RARα protein in leu kemi c cells from APL patients during the treatment, which is quite different from t hat during the treatment of ATRA.