RESUMEN
A comprehensive panel of clinical-biological parameters was prospectively evaluated at presentation in 112 patients with chronic lymphocytic leukemia (<65 years), to predict the risk of progression in early stage disease. Eighty-one percent were in Binet stage A, 19% in stages B/C. Treatment-free survival was evaluated as the time from diagnosis to first treatment, death or last follow up. In univariate analysis, advanced stage, hemoglobin, platelets, white blood cell, leukemic lymphocyte count, raised beta 2-microglobulin and LDH, unmutated immunoglobulin variable region genes, CD38, del(17p), del(11q) and +12, were significantly associated with a short treatment-free survival; the T/leukemic lymphocyte ratio was associated with a better outcome. Multivariate analysis of treatment-free survival in stage A patients selected a high white blood cell count and unmutated immunoglobulin variable region genes as unfavorable prognostic factors and a high T/leukemic lymphocyte ratio as a favorable one. At diagnosis, these parameters independently predict the risk of progression in stage A chronic lymphocytic leukemia patients.
Asunto(s)
Región Variable de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/genética , Mutación/genética , Adulto , Anciano , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genéticaAsunto(s)
Leucemia Mieloide/diagnóstico , Síndromes Mielodisplásicos/tratamiento farmacológico , Talidomida/análogos & derivados , Enfermedad Aguda , Anciano , Antineoplásicos/uso terapéutico , Transformación Celular Neoplásica/genética , Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Humanos , Lenalidomida , Leucemia Mieloide/genética , Masculino , Síndromes Mielodisplásicos/genética , Cariotipificación Espectral , Talidomida/uso terapéuticoRESUMEN
Since alterations in post-transcriptional events can contribute to the appearance and/or progression of cancer, we investigated whether RNA editing, catalyzed by the ADAR (adenosine deaminases that act on RNA) enzymes, is altered in pediatric astrocytomas. We find a decrease in ADAR2 editing activity that seems to correlate with the grade of malignancy in children. Despite the loss of ADAR2 editing activity in tumor tissues, the high grade astrocytomas do not exhibit alterations in ADAR2 expression when compared with their specific control tissues. However, high expression levels of ADAR1 and ADAR3 were found in tumors when compared with normal tissues dissected in the same area of the brain. We reintroduced either ADAR2 or the inactive version of ADAR2 in three astrocytoma cell lines (U118, A172, U87). The "reverted" editing status is necessary and sufficient for a significant decrease in cell malignant behavior as measured by proliferation, cell cycle, and migration assays. We show that elevated levels of ADAR1, as found in astrocytomas, do indeed interfere with ADAR2 specific editing activity. Furthermore, we show that the endogenous ADAR1 can form heterodimers with ADAR2 in astrocytes.
Asunto(s)
Adenosina Desaminasa/metabolismo , Astrocitoma/metabolismo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Adolescente , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Niño , Regulación hacia Abajo , Humanos , Ratones , Células 3T3 NIH , Edición de ARN , Proteínas de Unión al ARNRESUMEN
In this work, we used antibodies against histone H3 trimethylated at lysine 9 (H3K9m3); against histone H4 acetylated at lysines 5, 8, 12, and 16 (H4ac); and against DNA methylated at 5C cytosine (m5C) to study the presence and distribution of these markers in the genome of the isopod crustacean Asellus aquaticus. The use of these 3 antibodies to immunolabel spermatogonial metaphases yields reproducible patterns on the chromosomes of this crustacean. The X and Y chromosomes present an identical banding pattern with each of the antibodies. The heterochromatic telomeric regions and the centromeric regions are rich in H3K9m3, but depleted in m5C and H4ac. Thus, m5C does not seem to be required to stabilize the silence of these regions in this organism.
Asunto(s)
Metilación de ADN , Genoma , Histonas/metabolismo , Isópodos/genética , Isópodos/metabolismo , Acetilación , Animales , Anticuerpos/inmunología , Centrómero/química , Centrómero/metabolismo , Histonas/análisis , Histonas/inmunología , Masculino , Metilación , Espermatogonias/metabolismo , Telómero/química , Telómero/metabolismo , Cromosoma X/química , Cromosoma X/metabolismo , Cromosoma Y/química , Cromosoma Y/metabolismoRESUMEN
Four different units containing three variants of the U1 snRNA gene have been identified in the genome of Asellus aquaticus and only one unit has been identified in the genome of Proasellus coxalis. All four identified U1 snRNA genes can be folded according to the proper secondary structure and possess the functionally useful conserved sequences. Moreover, in the 3 flanking regions, all genes present both the 3 box, a conserved sequence required for 3 processing of mature snRNA, and a polyadenylation signal which is unusual for these genes. The PCR products were used as probes in fluorescent in-situ hybridization (FISH) experiments to locate them on chromosomes of A. aquaticus and P. coxalis.
