Mutant DNMT3A: a new marker of poor prognosis in acute myeloid leukemia
Menée sur 415 patients atteints d'une leucémie myéloïde aiguë, cette étude évalue l'association entre des mutations somatiques du gène DNMT3A et la survie des patients
The prevalence, the prognostic impact and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We demonstrate mutations in DNMT3A in 96/415 newly diagnosed AML patients (23.1%). Univariable Cox regression analysis demonstrated that DNMT3Amutant patients show significantly worse overall survival (OS:P=.022;hazard ratio [HR]=1.38;CI=1.04-1.81), and relapse-free survival (RFS:P=.005;HR=1.52;CI=1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavourable prognostic value as regards OS (P=.003;HR=1.82;CI=1.2-2.7) and RFS (P<.001;HR=2.2;CI=1.4-3.3) as well. In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations this association is particularly evident (OS:P=.013;HR=2.09;CI=1.16-3.77;RFS:P=.001;HR=2.65;CI=1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, since DNMT3Amutant AMLs did not express a methylation- or gene expression signature which discriminates them from DNMT3Awild-type AML patients. We conclude that DNMT3A mutation status is an important factor to consider for risk-stratification of AML patients.
Blood , résumé, 2012