Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy.
The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY. All CD34+ subpopulations expressed similar levels of mHAgs irrespective of disease phase, suggesting that in the SCT setting, mHAgs are the best target for GVL. Furthermore, WT1 was consistently overexpressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals. PRAME overexpression was limited to more mature AdP-CML progenitors only. Conversely, only CP-CML progenitors had PR3 overexpression, suggesting that PR1-peptide vaccines are only appropriate in CP-CML. Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients.
Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, M20892-1202, USA. yonga@nhlbi.nih.gov
A S M
AS
Yong
K
K
Keyvanfar
R
R
Eniafe
B N
BN
Savani
K
K
Rezvani
E M
EM
Sloand
J M
JM
Goldman
A J
AJ
Barrett
D018952:Antigens, CD34; D000951:Antigens, Neoplasm / Q000032:analysis*; D019496:Cancer Vaccines / Q000737:chemistry; D016022:Case-Control Studies; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology; D015778:Minor Histocompatibility Antigens / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000276:immunology*
D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins