【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。更多还原

【Abstract】 Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC-restricted cytotoxic activity of NK cells and facilitate specific allogeneic human cytotoxic T lymphocyte responses against fresh leukemia cells and cell lines. The Wilms’ tumor gene, WT1 mRNA, has been used as a marker of minimal residual disease (MRD) for evaluating therapeutic efficacy of patients with leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate whether in vitro IL-12 can lower WT1 gene expression in peripheral blood monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30 patients and 5 healthy volunteers were cultured at 5×10~5 cells/ml alone with or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than 10~3copies/μg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10~ 4.8 to 10~ 4.2 copies/μg of total RNA in 6 CML patients, from 10~ 5.4 to 10~ 4.8 copies/μg in 12 MDS patients and from 10~ 5.0 to 10~ 4.2 copies/μg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 may be of considerable benefit in the elimination of MRD in patients with hematological malignancies.更多还原