RESUMEN
Hypermethylation of the homeobox (HOX) gene promoter leads to decreased expression of the gene during tumor development and is thought to be correlated with the clinical outcome in leukemia. In this study, we performed pyrosequencing to quantify the methylation level of HOXA5 genes in the bone marrow samples obtained from 50 patients with AML and 19 normal controls. The methylation percentage of HOXA5 in AML patients (median=65.4%, interquartile range=35.9-72.3%) was higher than that of HOXA5 in control patients (median=43.1%, interquartile range=36.7-49.6%, Mann-Whitney U test, P=0.012). The patients of the AML group who had a high methylation percentage (>70%) had a good prognosis with a 3-yr overall survival (OS) of 82.5%, whereas the patients with a low methylation percentage (< or =70%) showed a 3-yr OS of 40.5% (P=0.048). Cox proportional hazards regression showed that the methylation percentages of HOXA5 were independently associated with the 3-yr OS of AML patients, regardless of their karyotypes. We propose that the quantification of HOXA5 methylation by pyrosequencing may be useful for predicting short-term prognosis in AML. However, the limitations of our study are the small sample size and its preliminary nature. Thus, a larger study should be performed to clearly determine the relationships among HOXA5 methylation levels, cytogenetics, and prognosis in AML patients.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metilación de ADN , Proteínas de Homeodominio/genética , Leucemia Mieloide Aguda/genética , Pronóstico , Regiones Promotoras Genéticas , Curva ROC , Análisis de Secuencia de ADN , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although most patients with cancer have a fatal outcome, it seems that the concern and study may be not enough. This study was aimed to perform the analysis of the cause of death, main symptom and treatment of the patients with terminal cancer and to provide the basic information about their adequate management. METHODS: We reviewed the medical records of 73 terminal cancer patients who had been managed with palliative therapy and died at Pusan National University Hospital from January 1999 to December 2001. The underlying malignant disease, ante-mortem symptoms, therapy and immediate cause of deaths were studied. RESULTS: A total 73 terminal cancer patients was included. The mean age was 53 years. Underlying malignant diseases were solid tumor (62%), acute myeloid leukemia (12%), non-Hodgkin's lymphoma (11%), chronic myeloid leukemia (10%), multiple myeloma (5%). The solid tumor was composed of gastrointestinal tract cancer (38%), head and neck cancer (13%), cancer of unknown primary site (9%), lung cancer (11%), hepatobiliary tract cancer (7%), cervical cancer (7%), ovarian cancer (4%), malignant melanoma (4%), soft tissue sarcoma and osteosarcoma (4%) and brain tumor (2%). The frequencies of the clinical complaints evaluated were the pain necessitating opiates, dyspnea (WHO grade >or=2), CNS disturbances, fever, hemorrhage, jaundice and intractable vomiting. Opiates, transfusions and antibiotics were the main therapy and pneumonia were the most important immediate causes of death. CONCLSUION: This results could be used as the basic information for the patients with terminal cancer and suggests a need for multi-center cooperation study.