首页|期刊导航|中华医学杂志（英文版）|Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation
中华医学杂志（英文版）2010，Vol.123Issue(7)：912-916,5.DOI:10.3760/cma.j.issn.0366-6999.2010.07.027
Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation
摘要
Abstract
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.关键词
cytotoxic T cells/Wilms' tumor 1 protein/graft-versus-leukemia effects/chronic myeloid leukemia/allogeneic hematopoietic stem cell transplantationKey words
cytotoxic T cells/Wilms' tumor 1 protein/graft-versus-leukemia effects/chronic myeloid leukemia/allogeneic hematopoietic stem cell transplantation引用本文复制引用
WANG Zhi-dong,LI Dan,HUANG Xiao-jun..Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation[J].中华医学杂志（英文版）,2010,123(7):912-916,5.基金项目
This work was supported by the grants from the Outstanding Youth Fund of Natural Science Foundation (No. 30725038), National 863 Hi-tech Project (No. IRT0702), Invocation Team Fund (No.2006AA02Z4A0) and the Ph.D. Programs Foundation of Ministry of Education of China(No.20060001108). （No. 30725038）
