Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Oncology Année : 2013

Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

Amélie Trinquand
  • Fonction : Auteur
Aline Tanguy-Schmidt
Raouf Ben Abdelali
  • Fonction : Auteur
Jérôme Lambert
  • Fonction : Auteur
Kheira Beldjord
  • Fonction : Auteur
Etienne Lengliné
  • Fonction : Auteur
Noémie de Gunzburg
  • Fonction : Auteur
Ludovic Lhermitte
Véronique Lhéritier
  • Fonction : Auteur
Jonathan Bond
  • Fonction : Auteur
Agnès Buzyn
  • Fonction : Auteur
Thibaud Leguay
  • Fonction : Auteur
Jean-Yves Cahn
  • Fonction : Auteur
Yves Chalandon
Caroline Bonmati
  • Fonction : Auteur
Sebastien Maury
  • Fonction : Auteur
Elizabeth Macintyre
Hervé Dombret

Résumé

PURPOSE: The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. PATIENTS AND METHODS: In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). RESULTS: N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). CONCLUSION: These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.

Domaines

Immunité innée

Dates et versions

hal-00979452 , version 1 (16-04-2014)

Identifiants

Citer

Amélie Trinquand, Aline Tanguy-Schmidt, Raouf Ben Abdelali, Jérôme Lambert, Kheira Beldjord, et al.. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.. Journal of Clinical Oncology, 2013, 31 (34), pp.4333-42. ⟨10.1200/JCO.2012.48.5292⟩. ⟨hal-00979452⟩
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