PMID- 20497687
OWN - NLM
STAT- MEDLINE
DCOM- 20100914
LR  - 20100525
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 123
IP  - 7
DP  - 2010 Apr 5
TI  - 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.
PG  - 912-6
AB  - 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.
FAU - Wang, Zhi-Dong
AU  - Wang ZD
AD  - Institute of Hematology, Peking University People's Hospital, Beijing 100044, 
      China.
FAU - Li, Dan
AU  - Li D
FAU - Huang, Xiao-Jun
AU  - Huang XJ
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (HLA Antigens)
RN  - 0 (WT1 Proteins)
SB  - IM
MH  - Adult
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Female
MH  - Genotype
MH  - HLA Antigens/genetics
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Immunologic Memory
MH  - Immunophenotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology/*therapy
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism
MH  - WT1 Proteins/*metabolism
MH  - Young Adult
EDAT- 2010/05/26 06:00
MHDA- 2010/09/15 06:00
CRDT- 2010/05/26 06:00
PHST- 2010/05/26 06:00 [entrez]
PHST- 2010/05/26 06:00 [pubmed]
PHST- 2010/09/15 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2010 Apr 5;123(7):912-6.