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Mutations of the epigenetics-modifying gene (DNMT3a, TET2, IDH1/2) at diagnosis may induce FLT3-ITD at relapse in de novo acute myeloid leukemia.
Wakita, S; Yamaguchi, H; Omori, I; Terada, K; Ueda, T; Manabe, E; Kurosawa, S; Iida, S; Ibaraki, T; Sato, Y; Todoroki, T; Hirakawa, T; Ryotokuji, T; Arai, K; Kitano, T; Mitamura, Y; Kosaka, F; Dan, K; Inokuchi, K.
Afiliação
  • Wakita S; Department of Internal Medicine, Division of Hematology, Nippon Medical School, Tokyo, Japan.
Leukemia ; 27(5): 1044-52, 2013 Apr.
Article em En | MEDLINE | ID: mdl-23135354
Gene mutations were found in acute myeloid leukemia (AML) and their importance has been noted. To clarify the importance and stability of mutations, we examined gene mutations in paired samples at diagnosis and relapse of 34 adult AML patients. Five acquired gene mutations were detected at relapse. Of the 45 gene mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations at relapse were all class I mutations as Fms-like tyrosine kinase 3 (FLT3) and rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3 of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1 (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at diagnosis is significantly higher than those in patients without them (P=0.001). Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases that initially present with any epigenetics-modifying gene mutations (P<0.001). Our results indicate that epigenetics-modifying gene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Proteínas Proto-Oncogênicas / DNA (Citosina-5-)-Metiltransferases / Proteínas de Ligação a DNA / Tirosina Quinase 3 Semelhante a fms / Isocitrato Desidrogenase / Mutação Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Proteínas Proto-Oncogênicas / DNA (Citosina-5-)-Metiltransferases / Proteínas de Ligação a DNA / Tirosina Quinase 3 Semelhante a fms / Isocitrato Desidrogenase / Mutação Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article