1. TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood.
- Author
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Coutinho DF, Monte-Mór BC, Vianna DT, Rouxinol ST, Batalha AB, Bueno AP, Boulhosa AM, Fernandez TS, Pombo-de-Oliveira MS, Gutiyama LM, Abdelhay E, and Zalcberg IR
- Subjects
- 5-Methylcytosine analogs & derivatives, Adolescent, Case-Control Studies, Child, Child, Preschool, Cytosine biosynthesis, DNA Mutational Analysis, DNA-Binding Proteins genetics, Dioxygenases, Female, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Mutation, Polymerase Chain Reaction, Proto-Oncogene Proteins genetics, Transcriptome, Cytosine analogs & derivatives, DNA-Binding Proteins biosynthesis, Gene Expression Regulation genetics, MicroRNAs genetics, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes metabolism, Proto-Oncogene Proteins biosynthesis
- Abstract
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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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