TY - JOUR
T1 - Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens
T2 - Implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy
AU - Yong, A. S.M.
AU - Keyvanfar, K.
AU - Eniafe, R.
AU - Savani, B. N.
AU - Rezvani, K.
AU - Sloand, E. M.
AU - Goldman, J. M.
AU - Barrett, A. J.
N1 - Funding Information:
We thank Ms Loretta Pfannes for technical advice on the assessment of WT1 surface protein by flowcytometry. This research was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute of the NIH.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=51649108782&partnerID=8YFLogxK
U2 - 10.1038/leu.2008.161
DO - 10.1038/leu.2008.161
M3 - Article
C2 - 18548092
AN - SCOPUS:51649108782
SN - 0887-6924
VL - 22
SP - 1721
EP - 1727
JO - Leukemia
JF - Leukemia
IS - 9
ER -