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

为了研究四硫化四砷(As4S4)对急性早幼粒细胞白血病(APL)患白血病细胞中PML/PML-RARα蛋白的作用。在患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使患体内APL细胞的PML/RML-RARα蛋白发生重新分布，与ATRA治疗后完全不同。

Change of PML/PML-RARα Protein during Treatment with Tetraarsenic Tetrasulfide (As4S4) in Patients with Acute Promyelocytic Leukemia

In order to explored the change of PML/PML-RARalpha protein during tetraarsenic tetrasulfide (As4S4) treatment, acute promyelocytic leukemia (APL) cells from a group of newly diagnosed APL patients were examined by indirect immunofluorescence staining with anit-PML monoclonal antibody. The results showed that all samples typically presented many microspeckle signals throughout the nucleus before treatment. The redistribution occurred as early as on the second day after As4S4 treatment, which revealed loss of microspeckles with the presentation of a few large speckles. Anti-PML staining also emerged in the perinuclear cytoplasm. At last, microspeckles and large speckles all disappeared. When the therapy was combining all-trans-retinoic acid (ATRA) with As4S4, similar results were obtained. However, APL cells from patients treated with ATRA alone performed totally different appearance, presenting microspeckles and large speckles at the same time, followed with entirely large speckles. The conclusion is that As4S4 makes redistribution of PML/PML-RARalpha protein in leukemic cells from APL patients during the treatment, which is quite different from that during the treatment of ATRA.