RESUMEN
The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16(-)CD56(+)-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56brightCD16dim/- NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.
Asunto(s)
Infecciones por Virus de Epstein-Barr/genética , Perfilación de la Expresión Génica , Hipersensibilidad/genética , Leucemia/genética , Linfoma de Células T/genética , Adolescente , Adulto , Anciano , Animales , Línea Celular Tumoral , Niño , Enfermedad Crónica , Análisis por Conglomerados , Culicidae/inmunología , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Ontología de Genes , Redes Reguladoras de Genes/genética , Humanos , Hipersensibilidad/inmunología , Mordeduras y Picaduras de Insectos/inmunología , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/patología , Leucemia/complicaciones , Leucemia/patología , Linfoma de Células T/complicaciones , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Transducción de Señal/genética , Adulto JovenRESUMEN
The Polycomb repressive complex-2 members (EZH2, EED, SUZ12 and EZH1) are important regulators of haematopoiesis, cell cycle and differentiation. Over-expression of EZH2 has been linked to cancer metastases and poor prognosis. Detailed information on the expression of other members in normal and neoplastic lymphoid tissue remains to be elucidated. Immunohistochemical and immunofluorescent analyses of 156 samples from haematopoietic neoplasms patients and 27 haematopoietic cell lines were used. B-cell neoplasms showed a significant over-expression of EZH2, EED and SUZ12 in the aggressive subtypes compared to the indolent subtypes and normal tissue (p = 0.000-0.046) while expression of EZH1 was decreased in mantle cell lymphoma compared to normal tissue (p = 0.011). T/NK-cell neoplasms also showed significant over-expression of EZH2, EED and SUZ12 (p = 0.000-0.002) and decreased expression of EZH1 (p = 0.001) compared to normal cells. EZH2 and EZH1 have opposite expression patterns both in normal and neoplastic lymphoid tissues as well as an opposite relation to Ki-67. These results were supported by western blotting analyses. Immunofluorescent staining revealed a difference in the intracellular localisation of EZH1 compared to other members. These evidences suggest that EZH2 and EZH1 are important in the counter-balancing mechanisms controlling proliferation/resting of lymphoid cells. The disruption of the balanced EZH2/EZH1 ratio may play important roles in the pathogenesis of lymphomas.
