白介素12降低白血病和骨髓增生异常综合征患者外周血单个核细胞WT1基因的表达_医学论文.docVIP

白介素12降低白血病和骨髓增生异常综合征患者外周血单个核细胞WT1基因的表达_医学论文 白介素12降低白血病和骨髓增生异常综合征患者外周血单个核细胞WT1基因的表达_医学论文 作者：潘崚，张学军，牛志云，索晓惠，张敬宇，杨琳， 刘小军，乔淑凯，董作仁，大野龙三【摘要】 有研究证实，白细胞介素12（IL-12）可以增强自然杀伤细胞的细胞毒性，还可以促进细胞毒T细胞对原代白血病细胞及白血病细胞株的细胞毒反应。此外，Wilms癌基因WT1 mRNA作为微小残留病变的标志已被广泛用于监测急性白血病（AL）和骨髓增生异常综合征（MDS）的疗效。为了研究IL-12能否降低AL和MDS患者外周血单个核细胞WT1基因的表达，分别收集了30例恶性血液病患者和5例健康志愿者的外周血单个核细胞（PBMNC）进行体外培养，在培养体系中加入IL-12。培养前和培养后第3天，用竞争性RT-PCR方法分别测定各标本中WT1 mRNA的表达量。结果显示，在6例慢性粒细胞性白血病患者，WT1 mRNA由104.8 降至104.2拷贝/微克总RNA；在12例MDS患者，WT1 mRNA由105.4降至104.8拷贝/微克总RNA；在5例完全缓解期AL患者，WT1 mRNA由105.0降至104.2拷贝/微克总RNA；但在7例未缓解的AL患者，WT1 mRNA的表达无变化。结论： IL-12可以显著降低大部分恶性血液病患者WT1 mRNA的表达水平，IL-12有望用于去除恶性血液病患者体内的微小残留病变。 【关键词】 白血病 　　Interleukin-12 (IL-12) is a heterodimeric cytokine produced by monocytes，B lymphocytes and other antigen-presenting cells under physiological conditions［1，2］. The names were initially given for the natural killer (NK) cell stimulatory factor or cytotoxic lymphocyte maturation factor based on its stimulatory effects on these cytotoxic lymphocyte populations. In vitro studies have demonstrated that IL-12 can enhance the non-MHC-restricted cytotoxic activity of NK cells［3］ and facilitate specific allogeneic human cytotoxic T lymphocyte responses against primary leukemia cells and cell lines［4-6］ . IL-12 can potently induce IFN-γ［7，8］，and up-regulate the expression of cytotoxic components including perforin，serine esterase and TIA-1 in peripheral blood lymphocytes［9］. IL-12 can also stimulate continuous proliferation of both T lymphocytes and NK cells［10］. 　　IL-12 has also been shown to have potent antitumor activities in murine tumor models，including B16F10 melanoma，renal cell adenocarcinoma，M5076 reticulum cell sarcoma，RAW117-H10 lymphoma and fibrosacoma［11-14］. In the RAW117-H10 lymphoma model，IL-12 showed a significant antitumor effect against metastatic lymphoma in the liver of lymphoma-bearing mice that had been treated with high-dose chemotherapy followed by stem cell transplantation，a situation which mimics clinical