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.
J Clin Oncol
; 31(34): 4333-42, 2013 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-24166518
ABSTRACT
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 ANDMETHODS:
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.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Análisis Mutacional de ADN
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Proteínas Proto-Oncogénicas
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Eliminación de Gen
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Proteínas ras
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Proteínas de Ciclo Celular
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Ubiquitina-Proteína Ligasas
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Proteínas F-Box
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Fosfohidrolasa PTEN
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Receptor Notch1
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Oncol
Año:
2013
Tipo del documento:
Article