TY - JOUR
T1 - Efficacious immune therapy in chronic myelogenous leukemia (CML) recognizes antigens that are expressed on CML progenitor cells
AU - Biernacki, Melinda A.
AU - Marina, Ovidiu
AU - Zhang, Wandi
AU - Liu, Fenglong
AU - Bruns, Ingmar
AU - Cai, Ann
AU - Neuberg, Donna
AU - Canning, Christine M.
AU - Alyea, Edwin P.
AU - Soiffer, Robert J.
AU - Brusic, Vladimir
AU - Ritz, Jerome
AU - Wu, Catherine J.
PY - 2010/2/1
Y1 - 2010/2/1
N2 - Curative effects of graft-versus-leukemia-based therapies such as donor lymphocyte infusion (DLI) for chronic myelogenous leukemia (CML) may result from immunologic ablation of self-renewing CML progenitor cells. Patients who achieved durable remissions after DLI developed a significant B-cell lymphocytosis after treatment, which did not occur in patients who were unresponsive to DLI. In this study, we identified antigen targets of this B-cell response by probing two immunoproteomic platforms with plasma immunoglobulins from seven CML patients with clinically apparent graft-versus-leukemia responses after DLI. In total, 62 antigens elicited greater reactivity from post-DLI versus pre-DLI plasma. Microarray analysis revealed that >70% of the antigens were expressed in CML CD34+ cells, suggesting that expression in malignant progenitor cells is a feature common to antibody targets of DLI. We confirmed elevated expression of three target antigens (RAB38, TBCE, and DUSP12) in CML that together consistently elicited antibody responses in 18 of 21 of an additional cohort of CML patients with therapeutic responses, but not in normal donors and rarely in non-CML patients. In summary, immunologic targets of curative DLI responses include multiple antigens on CML progenitor cells, identifying them as potential immunogens for vaccination and/or monitoring of immunotherapeutics designed to eliminate myeloid leukemia stem cells.
AB - Curative effects of graft-versus-leukemia-based therapies such as donor lymphocyte infusion (DLI) for chronic myelogenous leukemia (CML) may result from immunologic ablation of self-renewing CML progenitor cells. Patients who achieved durable remissions after DLI developed a significant B-cell lymphocytosis after treatment, which did not occur in patients who were unresponsive to DLI. In this study, we identified antigen targets of this B-cell response by probing two immunoproteomic platforms with plasma immunoglobulins from seven CML patients with clinically apparent graft-versus-leukemia responses after DLI. In total, 62 antigens elicited greater reactivity from post-DLI versus pre-DLI plasma. Microarray analysis revealed that >70% of the antigens were expressed in CML CD34+ cells, suggesting that expression in malignant progenitor cells is a feature common to antibody targets of DLI. We confirmed elevated expression of three target antigens (RAB38, TBCE, and DUSP12) in CML that together consistently elicited antibody responses in 18 of 21 of an additional cohort of CML patients with therapeutic responses, but not in normal donors and rarely in non-CML patients. In summary, immunologic targets of curative DLI responses include multiple antigens on CML progenitor cells, identifying them as potential immunogens for vaccination and/or monitoring of immunotherapeutics designed to eliminate myeloid leukemia stem cells.
UR - http://www.scopus.com/inward/record.url?scp=76249127539&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-09-2303
DO - 10.1158/0008-5472.CAN-09-2303
M3 - Article
C2 - 20103624
AN - SCOPUS:76249127539
SN - 0008-5472
VL - 70
SP - 906
EP - 915
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -
