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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WT1mRNA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WT1mRNA的表达量。结果显示,在6例慢性粒细胞性白血病患者,WT1mRNA由104.8降至104.2拷贝/微克总RNA;在12例MDS患者,WT1mRNA由105.4降至104.8拷贝/微克总RNA;在5例完全缓解期AL患者,WT1mRNA由105.0降至104.2拷贝/微克总RNA;但在7例未缓解的AL患者,WT1mRNA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WT1mRNA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。
Studies have shown that interleukin 12 (IL-12) can enhance the cytotoxicity of natural killer cells, but also can promote the cytotoxic T cells to primary leukemia cells and leukemia cell lines. In addition, Wilms oncoprotein WT1 mRNA, as a marker of minimal residual disease, has been widely used to monitor the efficacy of acute leukemia (AL) and myelodysplastic syndromes (MDS). In order to investigate whether IL-12 can reduce the expression of WT1 gene in peripheral blood mononuclear cells in patients with AL and MDS, peripheral blood mononuclear cells (PBMNC) from 30 patients with hematological malignancies and 5 healthy volunteers were collected for in vitro culture, IL-12 was added to the culture system. Before culturing and on the third day after culturing, the expression level of WT1 mRNA in each sample was determined by a competitive RT-PCR method. The results showed that in 6 patients with chronic myelogenous leukemia, the WT1 mRNA decreased from 104.8 to 104.2 copies / μg total RNA. In 12 MDS patients, the WT1 mRNA was decreased from 105.4 to 104.8 copies / μg total RNA. In 5 complete remission AL In patients, the WT1 mRNA was reduced from 105.0 to 104.2 copies / μg total RNA, but WT1 mRNA expression was unchanged in 7 unrelated AL patients. Conclusion: IL-12 can significantly reduce the expression of WT1mRNA in most hematologic malignancies, and IL-12 is expected to be used to remove minimal residual disease in patients with hematologic malignancies.