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Blood, 15 July 2007, Vol. 110, No. 2, pp. 770-775.
Prepublished online as a Blood First Edition Paper on April 5, 2007; DOI 10.1182/blood-2007-02-071738.
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Submitted February 2, 2007
Accepted April 3, 2007
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
Agnes SM Yong*, Katayoun Rezvani, Bipin N Savani, Rhoda Eniafe, Stephan Mielke, John M Goldman, and A John Barrett
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: yonga{at}nhlbi.nih.gov.
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 pre-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 7/27 HLA-identical sibling donors, and associated with improved LFS and OS post-SCT on follow-up. PR1-CTL responses detected in 7/28 CML patients pre-transplant 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 post-transplant outcome in AdP patients undergoing SCT. The presence of a donor immune response against PR1 may be advantageous and could be exploited therapeutically.
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