PMID- 21252986
OWN - NLM
STAT- MEDLINE
DCOM- 20110609
LR  - 20211020
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 25
IP  - 4
DP  - 2011 Apr
TI  - Improved outcome following allogeneic stem cell transplantation in chronic 
      myeloid leukemia is associated with higher expression of BMI-1 and immune 
      responses to BMI-1 protein.
PG  - 629-37
LID - 10.1038/leu.2010.325 [doi]
AB  - BMI-1 and EZH2 are polycomb group (PcG) proteins that maintain self-renewal of 
      stem cells, and are overexpressed in leukemia. To investigate the potential of 
      PcG proteins as leukemia-associated antigens, and as targets for 
      graft-versus-leukemia (GVL) effects, we studied cells obtained from 86 patients 
      with chronic myeloid leukemia (CML) and 25 human leukocyte antigen 
      (HLA)-A*0201(+) sibling donors collected before allogeneic stem cell 
      transplantation (SCT). Although BMI-1 overexpression in CD34(+) cells of CML 
      patients treated with pharmacotherapy is associated with poor prognosis, we 
      found, conversely, that in CML patients treated with SCT, a higher expression of 
      BMI-1, and correspondingly a lower expression of its target for repression, 
      CDKN2A, is associated with improved leukemia-free survival. Cytotoxic 
      T-lymphocyte (CTL) responses to the BMI-1 peptide were detected in 5 of 25 (20%) 
      donors, and in 8 of 19 (42%) HLA-A*0201(+) CML patients. BMI-1 generated more 
      total and high-avidity immune responses, and was more immunogenic than EZH2. 
      PcG-specific CTLs had a memory phenotype, were readily expanded in short-term 
      cultures and were detected after SCT in recipients of PcG-specific CTL-positive 
      donors. A higher BMI-1 expression in CML CD34(+) progenitors was associated with 
      native BMI-1 immune responses. These immune responses to PcG proteins may target 
      leukemia stem cells and have relevance for disease control by GVL.
FAU - Yong, A S M
AU  - Yong AS
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD 20892-1202, USA. yonga@nhlbi.nih.gov
FAU - Stephens, N
AU  - Stephens N
FAU - Weber, G
AU  - Weber G
FAU - Li, Y
AU  - Li Y
FAU - Savani, B N
AU  - Savani BN
FAU - Eniafe, R
AU  - Eniafe R
FAU - Keyvanfar, K
AU  - Keyvanfar K
FAU - Kurlander, R
AU  - Kurlander R
FAU - Rezvani, K
AU  - Rezvani K
FAU - Barrett, A J
AU  - Barrett AJ
LA  - eng
GR  - Z99 HL999999/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20110121
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD34)
RN  - 0 (BMI1 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.1.1.43 (Polycomb Repressive Complex 2)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
SB  - IM
MH  - Antigens, CD34/metabolism
MH  - Cohort Studies
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Graft vs Host Disease/*prevention & control
MH  - HLA-A Antigens
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Immunophenotyping
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology/metabolism/*therapy
MH  - Nuclear Proteins/genetics/*immunology/*metabolism
MH  - Peptide Fragments/immunology/metabolism
MH  - Polycomb Repressive Complex 1
MH  - Polycomb Repressive Complex 2
MH  - Proto-Oncogene Proteins/genetics/*immunology/*metabolism
MH  - RNA, Messenger/genetics
MH  - Repressor Proteins/genetics/*immunology/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Stem Cell Transplantation
MH  - Survival Rate
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transcription Factors/genetics/metabolism
MH  - Transplantation, Homologous
MH  - Treatment Outcome
PMC - PMC3076540
MID - NIHMS257150
COIS- Conflict of interest The authors have no competing financial interests in 
      relation to the work described.
EDAT- 2011/01/22 06:00
MHDA- 2011/06/10 06:00
PMCR- 2011/10/01
CRDT- 2011/01/22 06:00
PHST- 2011/01/22 06:00 [entrez]
PHST- 2011/01/22 06:00 [pubmed]
PHST- 2011/06/10 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - leu2010325 [pii]
AID - 10.1038/leu.2010.325 [doi]
PST - ppublish
SO  - Leukemia. 2011 Apr;25(4):629-37. doi: 10.1038/leu.2010.325. Epub 2011 Jan 21.