|
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 |
|