Publicaciones científicas

Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia

Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Navarro G, San Jose-Eneriz E, Garate L, Cordeu L, Cervantes F, Prosper F, Heiniger A, Torres A.
Hematology Department, Reina Sofia Hospital, Avda. Menendez Pidal s/n. 14004 Cordoba, Spain.

Revista: Haematologica

Fecha: 01-feb-2007

Área de Terapia Celular

BACKGROUND AND OBJECTIVES
Cancer 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 METHODS
In 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.

RESULTS
The 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.

CITA DEL ARTÍCULO  Haematologica. 2007 Feb;92(2):153-62

tal vezLE INTERESE

¿QUÉ TECNOLOGÍA UTILIZAMOS?

La Clínica es el hospital privado con mayor dotación tecnológica de España, todo en un único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

NUESTROS
PROFESIONALES

Los profesionales de la Clínica realizan una labor continuada de investigación y formación, siempre en beneficio del paciente.

Imagen profesionales de la Clínica Universidad de Navarra

POR QUÉ VENIR
A LA CLÍNICA

Conozca por qué somos diferentes a otros centros sanitarios. Calidad, rapidez, comodidad y resultados.

Imagen del edificio de la Clínica Universidad de Navarra