RESUMO
PURPOSE: Expression of the deleted in colorectal carcinoma (DCC) gene has been found to be lost in some patients with acute myelogenous leukemia (AML). Although this finding is critical to leukemogenesis, its prognostic significance remains uncertain. To evaluate this, loss of DCC gene expression in AML patients and their prognostic significance were investigated. EXPERIMENTAL DESIGN: A group of 170 patients with AML was analyzed. DCC gene expression in AML cells was determined by a semiquantitative reverse transcriptase-PCR. Simultaneous mutation analyses of the p53, N-ras, and FLT3 genes were performed in all of the AML cells by single-strand conformation polymorphism and sequencing subsequent to PCR. The importance of loss of DCC expression was evaluated by Cox proportional analysis and the Kaplan-Meier method. RESULTS: Loss of DCC expression was detected in 47 patients (27.6%). The p53, N-ras, and FLT3 mutations were detected in 20 (11.7%), 42 (24.7%), and 26 (15.2%) patients, respectively. The durations of overall survival (OS) and complete remission (CR) of the 47 DCC-negative AML patients were significantly shorter than that of the 123 DCC-positive patients (P < 0.0045 and <0.0060, respectively). Univariate and multivariate analyses showed that loss of DCC expression was an unfavorable prognostic factor for both OS (P < 0.0053 and <0.0084, respectively) and CR duration (P < 0.0146 and <0.0371, respectively). The 64 DCC-positive patients with wild p53, N-ras, and FLT3 had statistically better CR attainment compared with the other 106 patients (P < 0.0001). CONCLUSIONS: Loss of DCC gene expression was shown to be an independent prognostic factor in AML patients. Thus, loss of DCC gene expression might serve as an important molecular marker for predicting the CR duration and OS of patients with AML.
Assuntos
Genes DCC/genética , Leucemia Mieloide/genética , Doença Aguda , Adolescente , Adulto , Idoso , Medula Óssea/fisiologia , DNA de Neoplasias/genética , Progressão da Doença , Regulação para Baixo , Feminino , Expressão Gênica , Genes p53/genética , Genes ras/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Receptores Proteína Tirosina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Tirosina Quinase 3 Semelhante a fmsRESUMO
The bcl-x gene product has two forms, bcl-xl and bcl-xs. The bcl-xl form, similar to bcl-2, inhibits apoptosis. Reverse transcriptase-polymerase chain reaction/single-stranded conformation polymorphism (RT-PCR-SSCP) gel analysis was used to screen for mutations of the bcl-xl transcript of 50 non-Hodgkin's lymphoma (NHL) cases. One missense mutation in a patient with diffuse large B-cell lymphoma was found. Sequence analysis of this case showed that AGC (Ser) was mutated to GGC (Gly) in codon 154. An examination of mutation and/or polymorphism in born marrow samples of this case and 50 normal controls by the RT-PCR-SSCP method could not detect bandshifts. Mutation of the bcl-x gene in NHL has not been reported previously. There is a possibility that mutation of the bcl-x gene play a role in the tumorigenesis of NHL.