title: High PR3 or ELA2 expression by CD34+ cells in advanced-phase chronic myeloid leukemia is associated with improved outcome following allogeneic stem cell transplantation and may improve PR1 peptide-driven graft-versus-leukemia effects.
abstract: The primary granule proteins elastase (ELA2) and proteinase 3 (PR3) both contain the nonapeptide PR1, which can induce cytotoxic T lymphocyte (CTL) responses against chronic myeloid leukemia (CML) cells. To investigate whether eradication of CML after allogeneic stem cell transplantation (SCT) was influenced by PR3 and ELA2 gene expression or PR1-specific CTL responses, we studied cells from 87 CML patients and 27 HLA-A*0201(+) donors collected prior to T-cell-depleted HLA-identical sibling SCT. For patients in advanced phase (AdP), a higher expression of both PR3 and ELA2 in CD34(+) progenitors before SCT was associated with a lower incidence of relapse-related death, improved leukemia-free survival (LFS), and overall survival (OS); in chronic phase patients, no differences were observed. PR1-CTL responses were detected in 7 of 27 HLA-identical sibling donors, and associated with improved LFS and OS after SCT on follow-up. PR1-CTL responses detected in 7 of 28 CML patients before transplantation were not predictive of outcome and correlated inversely with PR3 and ELA2 expression. These findings suggest that assessment of PR3 and ELA2 expression in leukemic progenitors is useful for predicting posttransplantation outcome in AdP patients undergoing SCT. The presence of a donor immune response against PR1 may be advantageous and could be exploited therapeutically.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA. yonga@nhlbi.nih.gov
authors.forename: Agnes S M
authors.initials: AS
authors.lastname: Yong
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Rhoda
authors.initials: R
authors.lastname: Eniafe
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D018952:Antigens, CD34 / Q000502:physiology*; D005260:Female; D020544:Graft vs Leukemia Effect / Q000502:physiology*; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D008297:Male; D010447:Peptide Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000235:genetics*; D033581:Stem Cell Transplantation / Q000401:mortality; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C117309:pancreatic elastase II