CAJ | 학술논문

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WT1mRNA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.
유연구증실,백세포개소12(IL-12)가이증강자연살상세포적세포독성,환가이촉진세포독T세포대원대백혈병세포급백혈병세포주적세포독반응.차외,Wilms암기인WT1 mRNA작위미소잔류병변적표지이피엄범용우감측급성백혈병(AL)화골수증생이상종합정(MDS)적료효.위료연구IL-12능부강저AL화MDS환자외주혈단개핵세포WT1기인적표체,분별수집료30례악성혈액병환자화5례건강지원자적외주혈단개핵세포(PBMNC)진행체외배양,재배양체계중가입IL-12.배양전화배양후제3천,용경쟁성RT-PCR방법분별측정각표본중WT1mRNA적표체량.결과현시,재6례만성립세포성백혈병환자,WT1 mRNA유104.8강지104.2고패/미극총RNA;재12례MDS환자,WT1 mRNA유105.4강지104.8고패/미극총RNA;재5례완전완해기AL환자,WT1 mRNA유105.0강지104.2고패/미극총RNA;단재7례미완해적AL환자,WT1 mRNA적표체무변화.결론:IL-12가이현저강저대부분악성혈액병환자WT1 mRNA적표체수평,IL-12유망용우거제악성혈액병환자체내적미소잔류병변.
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 × 105 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 103copies/μg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from104.8 to 104.2 copies/μg of total RNA in 6 CML patients, from 105.4 to 104.8 copies/μg in 12 MDS patients and from105.0 to 104.2 copies/μg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12significantly 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.