Individualized therapy of patients with leukemia based on WT1 assay.

基于WT1检测的白血病患者个体化治疗。

• 批准号: 11670995
• 负责人: HIROYASU Ogawa
• 金额: $ 1.98万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670995/
• 关键词: leukemia; minimal residual disease; WT1; bone marrow transplantation; 微小残存白血病; キメラ遺伝子

We have reported that a high expression of WT1 gene is observed in almost all patients with leukemia, and that the detection of minimal residual disease (MRD) can be done in a sensitivity of 10^<-3> to 10^<-5> by the quantitation of WT1 gene expression levels on real-time PCR method. A low level of WT1 gene expression which is observed in CD34+ cells have been found to result in the background level expression of WT1 in bone marrow specimens. In this present study, the background levels of WT1 gene expression was found to reduce in one order in patients after bone marrow transplantation (BMT), by analyzing the WT1 gene expression in bone marrow samples in. which chimeric gene expressions could not be detected in RT-PCR analysis. These findings indicate that the sensitivity to detect MRD was increased after BMT.Furthermore, in the analysis of WT1 levels in patients who underwent BMT, a low level of WT1 gene expression before BMT, the HLA disparity between donors and recipients, and the presence of clinical graft-versus-host disease were found to be good prognostic factors to obtain a continuous complete remission.

我们已经报道了几乎所有白血病患者都观察到WT 1基因的高表达，并且通过实时PCR方法定量WT 1基因表达水平可以在10 μ g至10 μ g的灵敏度内检测微小残留病（MRD）<-3><-5>。已经发现在CD 34+细胞中观察到的低水平WT 1基因表达导致骨髓样本中WT 1的背景水平表达。在本研究中，WT 1基因表达的背景水平被发现在骨髓移植（BMT）后的患者中以一个顺序降低，通过分析WT 1基因在骨髓样本中的表达。RT-PCR分析不能检测到嵌合基因的表达。这些研究结果表明，检测MRD的敏感性增加后BMT。此外，在分析WT 1水平的患者进行BMT，低水平的WT 1基因表达BMT前，供者和受者之间的HLA差异，并存在临床移植物抗宿主病被认为是良好的预后因素，以获得持续的完全缓解。

项目成果

Tamaki H.et al.: "The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodyspastic syndromes"Leukemia. 13. 393-399 (1999)

Tamaki H.等人：“维尔姆斯肿瘤基因 WT1 是诊断骨髓痉挛综合征疾病进展的良好标志物”白血病。

Oji,Y. et al.: "Expression of the Wilms' tumor gene WT1 in solid tumors and its involovement in tumor cell growth."Japanese Journal of Cancer Research.. 90. 194-204 (1999)

王子，Y.

Oka, Y, et al.: "Cancer immunotherapy targeting Wilms' tumor gene WT1 product."Journal of Immunology. 164. 1873-1880 (2000)

Oka, Y 等人：“针对 Wilms 肿瘤基因 WT1 产物的癌症免疫疗法。”免疫学杂志。

Tsuboi,A. et al.: "Cytotoxic T lymphocyle responses elicited to wilms' tumor gene WT1 product by DNA vaccination."Journal of Clinical Immunology.. 20. 195-202 (2000)

坪井，A.

Tsuboi,A. et al.: "Cytotoxic T lymphocyte responses elicited to Wilms'tumor gene WT1 product by DNA vaccination."Journal of Clinical Immunology.. 20. 195-202 (2000)

坪井，A.