Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

DNMT3A mutation is associated with increased age and adverse outcome in adult T-acute lymphoblastic leukemia

Abstract :

The prognostic implications of DNMT3A genotype in T-ALL are incompletely understood. We performed comprehensive genetic and clinicobiological analyses of T-ALL patients with DNMT3A mutations treated during the GRAALL-2003 and -2005 studies. Eighteen of 198 cases (9.1%) had DNMT3A alterations. Two patients also had DNMT3A mutations in non-leukemic cell DNA, providing the first potential evidence of age-related clonal hematopoiesis in T-ALL. DNMT3A mutation was associated with older age (median 43.9 years v 29.4 years, p < 0.001), immature T-receptor genotype (53.3% v 24.4%, p = 0.016) and lower remission rates (72.2% mutated v 94.4% non-mutated, p = 0.006). DNMT3A alterations were significantly associated with worse clinical outcome, with higher cumulative incidence of relapse (CIR, HR 2.33, 95% CI 1.05-5.16, p = 0.037) and markedly poorer event-free survival (EFS, HR 3.22, 95% CI 1.81-5.72, p < 0.001) and overall survival (OS, HR 2.91, 95% CI 1.56-5.43, p = 0.001). Adjusting for age as a covariate, or restricting the analysis to patients over 40 years, who account for almost 90% of DNMT3A-mutated cases, did not modify these observations. In multivariate analysis using the risk factors that were used to stratify treatment during the GRAALL studies, DNMT3A mutation was significantly associated with shorter EFS (HR 2.33, 95% CI 1.06 - 4.04, p = 0.02). Altogether, these results identify DNMT3A genotype as a predictor of aggressive T-ALL biology. The GRAALL-2003 and -2005 studies were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.

Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-angers.fr/hal-02874597
Contributeur : Okina Université d'Angers <>
Soumis le : vendredi 19 juin 2020 - 02:50:59
Dernière modification le : jeudi 27 août 2020 - 09:01:51

Lien texte intégral

Identifiants

Citation

Jonathan Bond, Aurore Touzart, Stéphane Leprêtre, Carlos Graux, Mario Bargetzi, et al.. DNMT3A mutation is associated with increased age and adverse outcome in adult T-acute lymphoblastic leukemia. Haematologica, 2019, 104 (8), pp.1617-1625. ⟨10.3324/haematol.2018.197848⟩. ⟨hal-02874597⟩

Partager

Métriques

Consultations de la notice

62