Yamamoto Kouhei, Abe Shinya, Nakagawa Yasunori, Suzuki Kenshi, Hasegawa Maki, Inoue Miori, Kurata Morito, Hirokawa Katsuiku, Kitagawa Masanobu
Department of Pathology and Immunology, Aging and Developmental Sciences, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Japan.
Leuk Res. 2004 Nov;28(11):1203-11. doi: 10.1016/j.leukres.2004.03.020.
Bone marrow cells of patients with myelodysplastic syndromes (MDS) frequently undergo apoptosis, though the apoptotic cell ratio decreases when overt leukemia (OL) develops. Thus, we compared the expression of the inhibitor of apoptosis protein (IAP) gene family proteins in bone marrow samples from control, MDS, OL transformed from MDS (MDS --> OL), and de novo acute myelogenous leukemia (AML) subjects by the quantitative real-time RT-PCR method and an immunohistochemical approach. Overexpression of mRNA for survivin, cIAP1, NAIP and XIAP was significant in MDS bone marrow cells compared with control samples. However, the expression of mRNA for survivin, cIAP1 and cIAP2 exhibited a remarkable decrease after the development of OL (MDS --> OL). By immunohistochemistry, survivin was found to localize to the nucleus of myeloid cells in the majority of MDS cases. Next, the chronological changes in the expression of IAPs were determined in cases of MDS with evolution of OL. Although the expression of cIAP1 and cIAP2 revealed a sudden or gradual decrease as OL developed, survivin in many cases and XIAP in the majority of cases exhibited a peak of expression before a decline, indicating that these IAPs could be associated with the early events in the development of OL.
骨髓增生异常综合征（MDS）患者的骨髓细胞常发生凋亡，不过当进展为明显白血病（OL）时，凋亡细胞比例会降低。因此，我们采用定量实时逆转录聚合酶链反应（RT-PCR）方法和免疫组化方法，比较了对照组、MDS患者、由MDS转化而来的OL（MDS→OL）以及原发性急性髓系白血病（AML）患者骨髓样本中凋亡抑制蛋白（IAP）基因家族蛋白的表达情况。与对照样本相比，MDS骨髓细胞中survivin、cIAP1、NAIP和XIAP的mRNA表达显著上调。然而，在进展为OL（MDS→OL）后，survivin、cIAP1和cIAP2的mRNA表达显著下降。通过免疫组化发现，在大多数MDS病例中，survivin定位于髓系细胞的细胞核。接下来，在伴有OL进展的MDS病例中确定IAPs表达的时间变化。尽管随着OL的进展，cIAP1和cIAP2的表达突然或逐渐下降，但在许多病例中survivin以及在大多数病例中XIAP在下降之前都出现了表达高峰，这表明这些IAPs可能与OL发生发展的早期事件有关。
