期刊
BLOOD
卷 118, 期 19, 页码 5099-5107出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-02-334219
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资金
- Association Laurette Fugain
- Comite departement de la Ligue Contre le Cancer
- Ministere de l'Emploi et de la Solidarite, France
- Promoteur Hospices Civils de Lyon [PHRC 94-95-97.02]
- Ministere de l'Emploi et de la Solidarite, France [P0200701, P030425/AOM03081]
- Swiss Federal Government
Despite recent progress in the understanding of acute lymphoblastic leukemia (T-ALL) oncogenesis, few markers are sufficiently frequent in large subgroups to allow their use in therapeutic stratification. Low ERG and BAALC expression (E/B(low)) and NOTCH1/FBXW7 (N/F) mutations have been proposed as powerful prognostic markers in large cohorts of adult T-ALL. We therefore compared the predictive prognostic value of N/F mutations versus E/B(low) in 232 adult T-ALLs enrolled in the LALA-94 and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocols. The outcome of T-ALLs treated in the pediatric-inspired GRAALL trials was significantly superior to the LALA-94 trial. Overall, 43% and 69% of adult T-ALL patients were classified as E/B(low) and N/F mutated, respectively. Strikingly, the good prognosis of N/F mutated patients was stronger in more intensively treated, pediatric-inspired GRAALL patients. The E/expression level did not influence the prognosis in any subgroup. N/F mutation status and the GRAALL trial were the only 2 independent factors that correlated with longer overall survival by multivariate analysis. This study demonstrates that the N/F mutational status and treatment protocol are major outcome determinants for adults with T-ALL, the benefit of pediatric inspired protocols being essentially restricted to the N/F mutated subgroup. (Blood. 2011;118(19):5099-5107)
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