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Graft-versus-leukemia effects of WT1-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Wang zhidong 1 #,Li Dan 2,Huang xiaojun 1 *
1.Institute of Hematology and People’s Hospital, Peking University,
2.Institute of Hematology and People’s Hospital, Peking University,
*Correspondence author
#Submitted by
Subject:
Funding: none
Opened online:21 December 2009
Accepted by: none
Citation: Wang zhidong,Li Dan,Huang xiaojun.Graft-versus-leukemia effects of WT1-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation[OL]. [21 December 2009] http://en.paper.edu.cn/en_releasepaper/content/37796
 
 
The role of Wilms’ tumor 1 protein (WT1) - specific cytotoxic T cells (CTL) in eradicating chronic myeloid leukemia (CML) leukemia cells is to be established. This study is to determine whether WT1 contributes to graft-versus-leukemia effects (GVLE) for CML following allogeneic hematopoietic stem cell transplantation (HSCT). High-resolution 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.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 day 30,60,90 and 180,respectively. The median frequeny of WT1-CTL (1.38%) in patients with molecular remission (MoR) was significant higher than those without MoR (0.38%) on day 30, while no difference between them were detected on day 60,90 and 180. The increasement of WT1-CTL was associated with a decrease in bcr-abl expression and MoR and decrease of WT1-CTL was associated with a increase in bcr-abl expression, suggesting a WT1-driven GVL effect.WT1-CTL had a predominantly effector-memory phenotype (CD45RO+CD27-CD57+). Our results suggest the emergence of WT1-CTL with an effector-memory phenotype was associated with GVLE in CML patients after HSCT, which will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.
Keywords:cytotoxic T cells;Wilms’ tumor 1 protein;graft-versus-leukemia effects;chronic myeloid leukemia;allogeneic hematopoietic stem cell transplantation
 
 
 

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