RESUMO
Aims: Survivin is involved in the inhibition of apoptosis and the regulation of cell division. In addition to wild-type survivin (survivin-wt), at least four splice variants with differential functions (ΔEx3 and 3B antiapoptotic, and 2α and 2B proapoptotic) have been identified. Survivin is highly expressed in several cancers, including hematological malignancies. Although acute lymphoblastic leukemia (ALL) is the most frequent malignancy in children, studies that investigated survivin expression in ALL are limited, and there is no study on 3B and 2α expression in ALL. Therefore the expression of survivin-wt and its splice variants was investigated in pediatric B-cell ALL patients. Materials and Methods: The expression of survivin-wt and its four splice variants was investigated by quantitative real-time polymerase chain reaction in archival RNA samples of 35 pediatric B-cell ALL patients. Patients were divided into high- and standard-risk groups according to age, white blood cell count, extramedullary involvement, and genetic risk factors; expression of survivin variants was compared between these two risk groups. Results: We found that the ratio of survivin-ΔEx3/wild type (WT) expression was higher in the low-risk group than in the high-risk group. Conclusion: Comparative analysis between the high- and low-risk B-cell ALL groups indicated that the survivin-ΔEx3/WT expression ratio could potentially be used in risk classification for pediatric B-cell ALL.
Assuntos
Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Survivina/genética , Adolescente , Biomarcadores Tumorais , Criança , Pré-Escolar , Primers do DNA , Éxons/genética , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Lactente , Íntrons/genética , Masculino , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Risco , Survivina/biossínteseRESUMO
BACKGROUND/AIMS: The differential diagnosis of Wilson Disease (WD) is challenging, especially in children, because liver copper levels may also increase in other chronic liver diseases with bile stasis. The aim of this study is to determine urine and liver copper cut-off values to differentiate WD from other chronic liver diseases (non-WD, NWD) in children. MATERIALS AND METHODS: Seventy-six patients participated in the study, 35 with WD and 41 with NWD. The two groups were divided into two subgroups according to the presence of cholestasis. At the time of diagnosis, age, sex, biochemical test results, serum ceruloplasmin, baseline 24-h urinary copper levels, liver biopsy histological findings, liver copper levels, and Child-Pugh scores were obtained from medical records. Copper content in liver tissue and copper levels in urine were measured by atomic absorption spectrometry. Cut-off values for differentiation of WD from NWD were determined by receiver operating characteristic (ROC) analysis. RESULTS: A liver copper cut-off value of 98 µg/g indicated WD with 91% sensitivity and 65.4% specificity (area under the curve =0.838, 95% CI: 0.749-0.927). A 24-h urinary copper cut-off value of 67.5 µg/24h indicated WD with 85% sensitivity and 71% specificity (area under the curve =0.843, 95% CI: 0.752-0.934). CONCLUSION: In this study of pediatric chronic liver disease patients, copper cut-off values for distinguishing WD differed substantially from those used for diagnosis. A larger scale study is warranted to re-evaluate liver copper and 24-h urinary copper cut-offs for children with suspected WD.