RESUMEN
BACKGROUND/AIM: PON1 gene has an executive role in antioxidant defense, protecting cells from genotoxic factors. Q192R and L55M PON1 polymorphisms reduce catalytic activity of the encoded protein. These polymorphisms were studied in 300 chronic lymphocytic leukemia (CLL) patients and 106 healthy donors. They were also associated with patients' cytogenetic findings, to investigate their possible implication in CLL pathogenesis. MATERIALS AND METHODS: SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Karyotypic analysis was also performed by chromosome G-banding analysis and fluorescence in situ hybridization. RESULTS: Genotypic and allelic distribution of Q192R polymorphism showed a statistically significant higher frequency of mutant genotypes and mutant alleles in patients compared to controls. The same observation was noted in patients with abnormal karyotypes and those carrying abn14q32 and del(6q). A statistically increased frequency for the mutant allele was also revealed in patients with del(11q). On the contrary, L55M polymorphism showed a similar distribution between patients and controls. CONCLUSION: Q192R polymorphism plays a role in CLL predisposition and the formation of specific chromosomal aberrations.
Asunto(s)
Arildialquilfosfatasa/genética , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 6/genética , Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Aberraciones Cromosómicas , Femenino , Predisposición Genética a la Enfermedad , Técnicas de Genotipaje , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Persona de Mediana EdadRESUMEN
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by the presence of specific cytogenetic abnormalities. CLL research has been focused on epigenetic processes like gene promoter methylation of CpG islands. In the present study, the methylation status of the RAD21 gene is studied and associated with cytogenetic findings in CLL patients in order to investigate its possible implication in CLL pathogenesis and the formation of CLL chromosomal abnormalities.
Asunto(s)
Metilación de ADN , Leucemia Linfocítica Crónica de Células B/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Regiones Promotoras Genéticas , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Ciclo Celular , Análisis Citogenético , Proteínas de Unión al ADN , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q). ASXL1 mutations were also found in other genetically defined AML subgroups such as those with t(9;22), inv(3)/t(3;3), t(8;21) or t(15;17); however, none of our inv(16) cases carried ASXL1 mutations. We detected two previously unreported ASXL1 mutations, p.IIe593Val and p.Cys688Tyr. Our findings suggest that ASXL1 mutations tend to cluster with specific clinical and cytogenetic profiles of AML patients.