title: Frequent expression of HAGE in presentation chronic myeloid leukaemias.
abstract: Cancer testis (CT) antigens provide attractive targets for cancer-specific immunotherapy. Although CT genes are expressed in some normal tissues, such as the testis and in some cases placenta, these immunologically protected sites lack MHC I expression and as such, do not present 'self' antigens to T cells. To date, CT genes have been shown to be expressed in a range of solid tumours, but rarely in haematological malignancies. We have extended previous studies to investigate the expression of a comprehensive range of CT genes (MAGE-A1, -A3, -A6, -A12, BAGE, GAGE, HAGE,LAGE-1, NY-ESO-1 and RAGE) for their expression in a cohort of acute and chronic myeloid leukaemia patient samples. CT expression was not detected in 20 normal bone marrow or peripheral blood stem cell samples. In acute myeloid leukaemia (AML) nine of the 26 (35%) samples analysed expressed one or more of the CT genes with six of the samples (23%) expressing HAGE. In chronic myeloid leukaemia (CML) 24 of 42 (57%) presentation chronic myeloid leukaemia (CML) patient samples expressed one or more CT antigen with 23 expressing HAGE. We have shown that HAGE is frequently expressed in CML, and to a lesser extent in AML patient samples. This is the first demonstration of HAGE gene expression in myeloid leukaemia patients and the frequent expression of HAGE at disease presentation opens up the possibility of early immunotherapeutic treatments.
authors.affiliation: Leukaemia Science Laboratories, Department of Haematological Medicine, Guy's, King's & St Thomas' School of Medicine, Rayne Institute, London, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Adams
authors.forename: S S
authors.initials: SS
authors.lastname: Sahota
authors.forename: A
authors.initials: A
authors.lastname: Mijovic
authors.forename: B
authors.initials: B
authors.lastname: Czepulkowski
authors.forename: R A
authors.initials: RA
authors.lastname: Padua
authors.forename: G J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: B A
authors.initials: BA
authors.lastname: Guinn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D001854:Bone Marrow Cells / Q000502:physiology; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases; D004265:DNA Helicases; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C412324:DDX43 protein, human; D004265:DNA Helicases; D053487:DEAD-box RNA Helicases