背景 Wilm 的肿瘤的角色 1 蛋白质(WT1 ) 在根除的特定的细胞毒素的 T 房间(CTL ) 长期的 myeloid 白血病(电流型逻辑) 房间是被证实。这研究的目的是决定 WT1 是否为电流型逻辑后面的 allogeneic 贡献了 graft-versus-leukemia 效果(GVLE ) 造血的干细胞移植(HSCT ) 。方法高分辨率的人的白血球抗原(HLA ) 一级 genotyping 被顺序特定的聚合酶链反应(PCR ) 执行。经历了 allogeneic HSCT 的有电流型逻辑的十五个 HLA-A~*2402 病人在这研究被注册。我们由即时量的 PCR.Results 由 pentamer 试金和分子的最小的剩余疾病监视了 WT1 特定的 CTL 的频率对 WT1 的 CD8~+T 房间回答在 HSCT 以后在 15 个病人中的 14 个被观察。WT1-CTL 的中部的频率是 0.54% , 0.62% , 0.81% 和 1.28%(% CD8 ) 在天 30, 60, 90 和 180 分别地。当他们之间的重要差别都没在天被检测时,没有粗腐殖质(0.38%) ,在有分子的宽恕(粗腐殖质) 的病人的 WT1-CTL (1.38%) 的中部的频率在白天 30 上在那些比那显著地高 60, 90 和 180。WT1-CTL 的增加在 bcr-abl 表示和粗腐殖质与减少被联系;并且 WT1-CTL 的减少与 bcr-abl 表示的增加被联系,建议 WT1 驾驶 GVL 效果。WT1-CTL 有占优势的受动器记忆显型(CD45RO~+CD27~-CD57~+).Conclusions 有受动器记忆显型的 WT1-CTL 的出现在 HSCT 以后在电流型逻辑病人与 GVLE 被联系。这将铺平道路让 WT1 疫苗在电流型逻辑在 HSCT 以后提高 GVLE。
Background The role of Wilms' tumor 1 protein (WT1)-specific cytotoxic T cells (CTL) in eradicating chronic myeloid leukemia (CML) cells is to be established. The aim of this study was to determine whether WT1 contributed to the graft-versus-leukemia effects (GVLE) for CML following allogeneic hematopoietic stem cell transplantation (HSCT). Methods High-resolution human leukocyte antigen (HLA) class I genotyping was performed by sequence-specific polymerase chain reaction (PCR). Fifteen HLA-A~*2402 patients with CML who underwent allogeneic HSCT were enrolled in this study. We monitored the frequency of WT1-specific CTL by pentamer assay and the molecular minimal residual disease by real-time quantitative PCR.Results A CD8+ T-cell response to WT1 was observed in 14 of 15 patients after HSCT. The median frequencies of WT1-CTL were 0.54%, 0.62%, 0.81% and 1.28% (%CD8) on days 30, 60, 90 and 180, respectively. The median frequency of WT1-CTL (1.38%) in patients with molecular remission (MoR) was significantly higher than that in those without MoR (0.38%) on day 30, while no significant differences between them were detected on days 60, 90 and 180. The increase of WT1-CTL was associated with a decrease in bcr-abl expression and MoR; and the decrease of WT1-CTL was associated with an increase in bcr-abl expression, suggesting a WT1 -driven GVL effect. WT1-CTL had a predominant effector-memory phenotype (CD45RO+CD27-CD57+).Conclusions The emergence of WT1-CTL with an effector-memory phenotype is associated with GVLE in CML patients after HSCT. This will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.