RT Journal Article
T1 Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia.
A1 Roman-Gomez, Jose
A1 Jimenez-Velasco, Antonio
A1 Agirre, Xabier
A1 Castillejo, Juan A
A1 Navarro, German
A1 San Jose-Eneriz, Edurne
A1 Garate, Leire
A1 Cordeu, Lucia
A1 Cervantes, Francisco
A1 Prosper, Felipe
A1 Heiniger, Anabel
A1 Torres, Antonio
K1 Cancer testis antigens
K1 Hypomethylation
K1 CML
K1 HAGE
K1 Leucemia mielogenosa crónica BCR-ABL positiva
K1 Regiones promotoras genéticas
K1 Interferones
K1 Pirimidinas
K1 Metilación del ADN
AB BACKGROUND AND OBJECTIVESCancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy. Although CTA genes are expressed in some normal tissues, such as the testis, this immunologically protected site lacks MHC I expression and as such, does not present self antigens to T cells. To date, CTA genes have been shown to be expressed in a range of solid tumors via demethylation of their promoter CpG islands, but rarely in chronic myeloid leukemia (CML) or other hematologic malignancies.DESIGN AND METHODSIn this study, the methylation status of the HAGE CTA gene promoter was analyzed by quantitative methylation-specific polymerase chain reaction (MSP) and sequencing in four Philadelphia-positive cell lines (TCC-S, K562, KU812 and KYO-1) and in CML samples taken from patients in chronic phase (CP n=215) or blast crisis (BC n=47). HAGE expression was assessed by quantitative reverse transcriptase-polymerase chain reaction.RESULTSThe TCC-S cell line showed demethylation of HAGE that was associated with over-expression of this gene. HAGE hypomethylation was significantly more frequent in BC (46%) than in CP (22%) (p=0.01) and was correlated with high expression levels of HAGE transcripts (p<0.0001). Of note, in CP-CML, extensive HAGE hypomethylation was associated with poorer prognosis in terms of cytogenetic response to interferon (p=0.01) or imatinib (p=0.01), molecular response to imatinib (p=0.003) and progression-free survival (p=0.05). INTERPRETATIONS AND CONCLUSION: The methylation status of the HAGE promoter directly correlates with its expression in both CML cell lines and patients and is associated with advanced disease and poor outcome.
PB Ferrata Storti Foundation
SN 0390-6078
YR 2007
FD 2007-02
LK http://hdl.handle.net/10668/1285
UL http://hdl.handle.net/10668/1285
LA en
NO Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Navarro G, San Jose-Eneriz E, et al. Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia. Haematologica. 2007                         ; 92(2):153-62
NO Journal Article;
DS RISalud
RD Apr 10, 2025