Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Blood Année : 2015

Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL

Romain Guièze
  • Fonction : Auteur
Sophie De Guibert
  • Fonction : Auteur
Bruno Pereira
Maite Cabes
  • Fonction : Auteur
Adam Burns
  • Fonction : Auteur
Andrew Pettitt
  • Fonction : Auteur
Peter Hillmen
  • Fonction : Auteur
  • PersonId : 902507

Résumé

Although TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in prospective trials was screened using targeted next-generation sequencing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes. We performed clustering according to both number and combinations of recurrent gene mutations. The number of genes affected by mutation was ≥2, 1, and 0 in 43 (38%), 49 (43%), and 22 (19%) respectively. Recurrent combinations of ≥2 mutations of TP53, SF3B1, and ATM were found in 22 (19%) patients. This multiple-hit profile was associated with a median progression-free survival of 12 months compared with 22.5 months in the remaining patients (P = .003). Concurrent gene mutations are frequent in patients with relapsed/refractory CLL and are associated with worse outcome

Dates et versions

hal-01263113 , version 1 (27-01-2016)

Identifiants

Citer

Romain Guièze, Pauline Robbe, Ruth Clifford, Sophie De Guibert, Bruno Pereira, et al.. Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. Blood, 2015, 126 (18), pp.2110--2117. ⟨10.1182/blood-2015-05-647578⟩. ⟨hal-01263113⟩
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