Assuntos
Ataxia Telangiectasia/diagnóstico , Linfoma de Burkitt/diagnóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/genética , Linfoma de Burkitt/complicações , Linfoma de Burkitt/genética , Criança , Cromossomos Humanos Par 8 , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Masculino , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , TrissomiaRESUMO
Myelodysplastic syndromes (MDS) are myeloid malignancies characterized by ineffective hematopoiesis, dysplasia, peripheral cytopenia and increased risk of progression to acute myeloid leukemia. Refractory cytopenia of childhood (RCC) is the most common subtype of pediatric MDS and has overlapping clinical features with viral infections and autoimmune disorders. Mutations in TET2 gene are found in about 20-25% of adult MDS and are associated with a decrease in 5-hydroxymethylcytosine (5-hmC) content. TET2 deregulation and its malignant potential were reported in adult but not in pediatric MDS. We evaluated the gene expression and the presence of mutations in TET2 gene in 19 patients with RCC. TET2 expression level was correlated with 5-hmC amount in DNA and possible regulatory epigenetic mechanisms. One out of 19 pediatric patients with RCC was a carrier of a TET2 mutation. TET2 expression and 5-hmC levels were decreased in patients when compared to a disease-free group. Lower expression was not associated to the presence of mutation or with the status of promoter methylation, but a significant correlation with microRNA-22 expression was found. These findings suggested that TET2 downregulation and low levels of 5-hmC are inversely related to miR-22 expression. The existence of a regulatory loop between microRNA-22 and TET2 may play a role in MDS pathogenesis.
Assuntos
Citosina/análogos & derivados , Proteínas de Ligação a DNA/biossíntese , Regulação da Expressão Gênica/genética , MicroRNAs/genética , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , 5-Metilcitosina/análogos & derivados , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Citosina/biossíntese , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Dioxigenases , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Mutação , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/genética , TranscriptomaRESUMO
Infants diagnosed with acute myelogenous leukemia (AML) are likely to have subtypes M4 or M5 characterized by 11q23 abnormalities like a t(9;11)(p22;q23). Detection of all possible types of chromosomal abnormalities, including mixed lineage leukemia (MLL) gene rearrangements at 11q23, is of importance for the identification of biological subgroups, which might differ in drug resistance and/or clinical outcome. Here, we report the clinical, conventional banding and molecular cytogenetics data of a 6-month-old boy with an AML-M5 presenting with a unique cryptic rearrangement involving the MLL gene: a three-way t(9;19;11)(p11.2;p13.1;q23).