mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies.
Specific immunotherapies for patients with acute myeloid leukemia (AML) using leukemia-associated antigens (LAA) as target structures might be a therapeutic option to enhance the graft-vs.-leukemia effect observed after allogeneic stem cell transplantation or to prolong a complete remission (CR) achieved by chemotherapy. Significant mRNA expression of LAA is a prerequisite for such immunotherapies. Here, previously characterized antigens associated with solid tumors (TAA) and newly characterized LAA were investigated for their expression in up to 60 AML patients and in leukemia cell lines. To investigate their specificity for leukemic blasts, the mRNA expression was also characterized in PBMN and CD34 positive cells of healthy volunteers and in a panel of normal tissues. The following antigens showed high mRNA expression in AML patients: MPP11 was detected in 43/50 (86%), RHAMM in 35/50 (70%), WT1 in 40/60 (67%), PRAME in 32/50 (64%), G250 in 18/35 (51%), hTERT in 7/25 (28%) and BAGE in 8/30 (27%) of AML patients. Real-time RT-PCR showed a tumor-specific expression of the antigens BAGE, G250 and hTERT, as well as highly tumor-restricted expression for RHAMM, PRAME and WT1. The antigen MPP11 was overexpressed. These antigens might be candidates for immunotherapies of leukemia patients and, because of their simultaneous expression, also for polyvalent vaccines.
Greiner
Jochen
J
Third Department of Medicine, University of Ulm, Ulm, Germany.
Ringhoffer
Mark
M
Taniguchi
Masanori
M
Li
Li
L
Schmitt
Anita
A
Shiku
Hiroshi
H
Döhner
Hartmut
H
Schmitt
Michael
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm