TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood.
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.
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Diego F
DF
Coutinho
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Bárbara C R
BC
Monte-Mór
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil; Setor de Hematologia Pediátrica, Serviço de Pediatria, Hospital Federal da Lagoa, Rio de Janeiro, RJ, Brazil.
Danielle T
DT
Vianna
Setor de Hematologia Pediátrica, Serviço de Pediatria, Hospital Federal da Lagoa, Rio de Janeiro, RJ, Brazil.
Soraia T
ST
Rouxinol
Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Anna Beatriz W
AB
Batalha
Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Ana Paula S
AP
Bueno
Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Alice M
AM
Boulhosa
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Teresa S
TS
Fernandez
Programa de Hematologia e Oncologia Pediátricos, Centro de Pesquisas (CPQ), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Maria S
MS
Pombo-de-Oliveira
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Luciana M
LM
Gutiyama
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Eliana
E
Abdelhay
Divisão de Laboratórios do Centro de Transplantes de Medula Óssea (CEMO), Instituto Nacional do Câncer (INCA), Rio de Janeiro, RJ, Brazil. Electronic address: zalcberg@inca.gov.br.
Ilana R
IR
Zalcberg
D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003596:Cytosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D049308:Dioxygenases; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D059467:Transcriptome
D004268:DNA-Binding Proteins; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C541081:TET2 protein, human
Epigenetics; Myelodysplastic syndrome; Pediatrics; Refractory cytopenia of childhood; TET2