Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia.

Abstract:

:The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3A(mutant) AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3A(wild-type) AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). 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; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3A(mutant) AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3A(wild-type) AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

journal_name

Blood

journal_title

Blood

authors

Ribeiro AF,Pratcorona M,Erpelinck-Verschueren C,Rockova V,Sanders M,Abbas S,Figueroa ME,Zeilemaker A,Melnick A,Löwenberg B,Valk PJ,Delwel R

doi

10.1182/blood-2011-07-367961

subject

Has Abstract

pub_date

2012-06-14 00:00:00

pages

5824-31

issue

24

eissn

0006-4971

issn

1528-0020

pii

blood-2011-07-367961

journal_volume

119

pub_type

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