title: Ten-eleven-translocation 2 (TET2) is downregulated in myelodysplastic syndromes.
abstract: TET2, a member of the ten-eleven-translocation (TET) family genes that modify DNA by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is located in chromosome 4q24 and is frequently mutated in myeloid malignancies. The impact of TET2 mutation on survival outcomes is still controversial; however, functional studies have proved that it is a loss-of-function mutation that impairs myeloid cell differentiation and contributes to the phenotype of myeloid neoplasia. We, herein, aimed to investigate TET2 expression in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A significantly decreased TET2 expression was observed in bone marrow cells from AML (n = 53) and patients with MDS (n = 64), compared to normal donors (n = 22). In MDS, TET2 expression was significantly reduced in RAEB-1/RAEB-2 compared to other WHO 2008 classifications, and a lower TET2 expression was observed at the time of MDS disease progression in four of five patients. In multivariate analysis, low TET2 expression (P = 0.03), male gender (P = 0.02), and WHO 2008 classification (P < 0.0001) were independent predictors of poorer overall survival. These results suggest that defective TET2 expression plays a role in the MDS pathophysiology and predicts survival outcomes in this disease.
authors.affiliation: Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, SP, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Scopim-Ribeiro
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
authors.forename: Paula de Melo
authors.initials: Pde M
authors.lastname: Campos
authors.forename: Cleide Aparecida Moreira
authors.initials: CA
authors.lastname: Silva
authors.forename: Patricia
authors.initials: P
authors.lastname: Favaro
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.forename: Sara Teresinha Olalla
authors.initials: ST
authors.lastname: Saad
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000756:Anemia, Sideroblastic / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: acute myeloid leukemia; myelodysplastic syndromes; ten-eleven-translocation 2