Expression of RHAMM/CD168 and other tumor-associated antigens in patients with B-cell chronic lymphocytic leukemia.
Antigen targeted immunotherapies might represent a novel treatment for B-cell chronic lymphocytic leukemia (B-CLL). We screened the mRNA expression of tumor-associated antigens (TAAs) from the literature (fibromodulin, survivin, OFA-iLRP, BAGE, G250, MAGE1, PRAME, proteinase, syntaxin, hTERT, WT-1) and TAAs defined previously by serological analysis of cDNA expression libraries from leukemic cells (PINCH, HSJ2, MAZ, MPP11, RHAMM/CD168, NY-Ren60). Peripheral blood mononuclear cells from 43 B-CLL patients and 20 healthy volunteers (HVs) were examined by conventional and quantitative RT-PCR. mRNA of RHAMM/CD168, fibromodulin, syntaxin and NY-Ren60 was expressed in 55-90%, and mRNA of HSJ2, MAZ and OFAiLRP was expressed in 90-100% of the patients. No expression of WT-1, hTERT, BAGE, G250, MAGE1 or survivin was observed. Low (2-20%) expression frequencies of MPP11, PINCH, PRAME and proteinase were detected. RHAMM/CD168, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. Because of the exquisite tissue expression of RHAMM/CD168 and its high expression frequency in CLL patients, mixed lymphocyte peptide culture (MLPC), enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry were performed for antigen specific T-cells. In MLPC, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RAhigh effector T-cells were detected. RHAMM/CD168 might be a possible target for future immunotherapies in both ZAP-70(+) and ZAP-70(-) B-CLL patients.
Giannopoulos
K
K
Department of Internal Medicine III, University of Ulm, D-89081 Ulm, Germany.
Li
L
L
Bojarska-Junak
A
A
Rolinski
J
J
Dmoszynska
A
A
Hus
I
I
Greiner
J
J
Renner
C
C
Döhner
H
H
Schmitt
M
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D000071235:Fibromodulin; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009842:Oligopeptides / Q000276:immunology; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D018960:Hyaluronan Receptors; D018832:Molecular Chaperones; D009842:Oligopeptides; D015513:Oncogene Proteins; C404944:PRAME protein, human; D011509:Proteoglycans; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C098946:hyaluronan-mediated motility receptor; D000071235:Fibromodulin; D051746:ZAP-70 Protein-Tyrosine Kinase