PMID- 9924693
OWN - NLM
STAT- MEDLINE
DCOM- 19990325
LR  - 20191102
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 22
IP  - 1
DP  - 1999 Jan
TI  - Donor-recipient polymorphism of the proteinase 3 gene: a potential target for 
      T-cell alloresponses to myeloid leukemia.
PG  - 1-6
AB  - The curative effect of allogeneic bone marrow transplantation (BMT) is in part 
      due to an alloresponse of donor lymphocytes against recipient leukemia termed the 
      graft versus leukemia (GvL) effect. To identify target antigens for the GvL 
      response on leukemia cells, we looked for polymorphism of proteinase 3, a primary 
      granule protein overexpressed in myeloid leukemias. The study was carried out in 
      10 patients with hematologic diseases and their HLA-identical marrow donors. By 
      polymerase chain reaction (PCR)-single strand conformation polymorphism assay, 
      followed by direct sequencing of the PCR products, we found seven DNA 
      polymorphisms. One of them encodes for either an isoleucine or a valine at 
      position 119 of the amino acid sequence. Peptides that span the polymorphic site, 
      at amino acids 115-124, were shown to bind in vitro to the HLA-A2 molecule. We 
      screened 23 HLA-A2 patients with myeloid leukemia and their HLA-identical donors 
      for this polymorphism. No relapse was found in the group of 4 evaluable patients 
      who possessed at least one allele absent in their donor, whereas 7 of the 15 
      remaining evaluable patients relapsed. These data support the possibility that 
      T-cell responses to allelic differences of proteinase 3 could be used as a basis 
      for designing leukemia-specific adoptive T-cell therapy in acute and chronic 
      myeloid leukemias.
FAU - Clave, E
AU  - Clave E
AD  - Bone Marrow Transplantation Unit, Hematology Branch, National Heart, Lung and 
      Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1652, 
      USA.
FAU - Molldrem, J
AU  - Molldrem J
FAU - Hensel, N
AU  - Hensel N
FAU - Raptis, A
AU  - Raptis A
FAU - Barrett, A J
AU  - Barrett AJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (HLA-A Antigens)
RN  - 0 (Peptide Fragments)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.76 (Myeloblastin)
SB  - IM
MH  - Alleles
MH  - *Bone Marrow Transplantation
MH  - Exons/genetics
MH  - Female
MH  - Flow Cytometry
MH  - Gene Frequency
MH  - Genotype
MH  - *Graft vs Tumor Effect
MH  - HLA-A Antigens/genetics/immunology/metabolism
MH  - Histocompatibility Testing
MH  - Humans
MH  - Leukemia, Myeloid/genetics/immunology/*therapy
MH  - Male
MH  - Myeloblastin
MH  - Peptide Fragments/genetics/immunology/metabolism
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - Protein Binding
MH  - Recurrence
MH  - Serine Endopeptidases/*genetics/immunology/metabolism
MH  - T-Lymphocytes/immunology/metabolism
MH  - *Tissue Donors
EDAT- 1999/01/30 00:00
MHDA- 1999/01/30 00:01
CRDT- 1999/01/30 00:00
PHST- 1999/01/30 00:00 [pubmed]
PHST- 1999/01/30 00:01 [medline]
PHST- 1999/01/30 00:00 [entrez]
AID - 10.1097/00002371-199901000-00001 [doi]
PST - ppublish
SO  - J Immunother. 1999 Jan;22(1):1-6. doi: 10.1097/00002371-199901000-00001.