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Clinical implications of DNMT3A mutations in a Southeast Asian cohort of acute myeloid leukaemia patients.
Tan, Marcus; Ng, Isaac K S; Chen, Zhaojin; Ban, Kenneth; Ng, Christopher; Chiu, Lily; Seah, Elaine; Lin, Mingxuan; Tai, Bee Choo; Yan, Benedict; Ng, Chin Hin; Chng, Wee-Joo.
Afiliación
  • Tan M; Department of Biochemistry, National University of Singapore, Singapore, Singapore.
  • Ng IKS; Department of Biochemistry, National University of Singapore, Singapore, Singapore.
  • Chen Z; Investigational Medicine Unit, National University Health System, Singapore, Singapore.
  • Ban K; Department of Biochemistry, National University of Singapore, Singapore, Singapore.
  • Ng C; Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, Singapore, Singapore.
  • Chiu L; Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, Singapore, Singapore.
  • Seah E; Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System, Singapore, Singapore.
  • Lin M; Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, Singapore, Singapore.
  • Tai BC; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
  • Yan B; Department of Laboratory Medicine, Molecular Diagnosis Centre, National University Health System, Singapore, Singapore.
  • Ng CH; Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System, Singapore, Singapore.
  • Chng WJ; Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System, Singapore, Singapore.
J Clin Pathol ; 70(8): 669-676, 2017 Aug.
Article en En | MEDLINE | ID: mdl-28100593
AIMS: In recent years, genomic technologies have enabled the identification of mutations in acute myeloid leukaemia (AML). DNMT3A is a recurrently mutated epigenetic modifier gene in AML. To date, the prognostic significance of DNMT3A mutations has not been studied in a Southeast Asian AML population. We sought to investigate the clinical implications of DNMT3A mutations in a Southeast Asian cohort of AML patients. METHODS: DNMT3A mutations were identified using a targeted next-generation sequencing panel in 157 AML patients. We studied the molecular and clinical features of patients with DNMT3A mutations and assessed the prognostic impact of DNMT3A mutations. RESULTS: DNMT3A mutations were found in 33 of 157 (21.0%) AML patients. 114 patients were included for statistical analysis. Pretreatment data revealed that patients with DNMT3A mutations were older (≥60 years old), had a higher white blood cell count at diagnosis, had more adverse cytogenetic risk profiles and were more often associated with NPM1 mutations compared with patients with wild-type DNMT3A. Survival analysis showed that DNMT3A mutations were associated with poorer clinical outcomes. This was especially when associated with NPM1 and FLT3-ITD mutations (AML NPM1/FLT3/DNMT3A ), which are common. The AML NPM1/FLT3/DNMT3A subtype was an independent predictor for poorer overall survival (OS). Other independent risk factors for poorer OS include advanced age at diagnosis and adverse cytogenetic risk stratification. CONCLUSIONS: DNMT3A mutations are associated with an unfavourable clinical outcome in our Southeast Asian AML patient cohort. In particular, AML NPM1/FLT3/DNMT3A patients had the poorest prognosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / ADN (Citosina-5-)-Metiltransferasas / Mutación Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: J Clin Pathol Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / ADN (Citosina-5-)-Metiltransferasas / Mutación Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: J Clin Pathol Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido