Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence
Menée sur plusieurs cohortes de patients pédiatriques atteints d'une leucémie lymphoblastique T, cette étude évalue l'intérêt de la recherche de mutations du gène NOTCH1 et du statut LOH6q pour le pronostic de la maladie
Event-free survival (pEFS) in pediatric T-cell lymphoblastic lymphoma (T-LBL) is about 80%, whereas survival in relapsed patients is 10-15%. No stratification criteria are established allowing the modulating of treatment intensity. Recently, activating NOTCH1 mutations were reported to be associated with favorable prognosis. And loss of heterozygosity at chromosome 6q (LOH6q) was reported to be associated with increased relapse risk. The current project aimed at evaluating the prognostic impact of these genetic markers. One hundred-sixteen patients were analyzed for mutations in hotspots of NOTCH1 and FBXW7. Concerning LOH6q status, 118 patients were investigated using conventional microsatellite marker analysis in addition to an earlier reported test cohort of 99 available patients. Ninety-two cases were evaluable for both analyses. All patients were registered in the NHL-BFM study center and treated with ALL-BFM-type treatment. LOH6q was observed in 12% of patients (25/217). pEFS was 27±9% for patients with LOH6q compared to 86±3% for LOH6q negative patients (p<0.0001). In 60% (70/116) NOTCH1 mutations were detected and associated with favorable prognosis (pEFS 84±5% versus 66±7%, p=0.021). Interestingly, NOTCH1 mutations were rarely observed in patients with LOH in 6q16. Both prognostic markers, NOTCH1 mutations and LOH6q, will be used as stratification criteria in coming NHL-BFM trials.
Blood , résumé, 2013