Mutations in the Toll-like receptor/MYD88 pathway in chronic lymphocytic leukemia identify a subset of young patients with favorable outcome
Menée sur des échantillons prélevés sur 587 patients atteints d'une leucémie lymphocytaire chronique, cette étude identifie des mutations des gènes MYD88 et du récepteur Toll-like en association avec un pronostic favorable chez les patients d'âge inférieur à 50 ans
Mutations in Toll-like receptor and MYD88 genes (TLR/MYD88) have been found in chronic lymphocytic leukemia (CLL) at low frequency. We analyzed the incidence, clinicobiological characteristics and outcome of patients with mutations in TLR/MYD88 in 587 CLL patients by either whole-exome or Sanger sequencing. Twenty-three patients (3.9%) had mutations, 19 in MYD88 (one with concurrent IRAK1 mutation), 2 TLR2 (one with concomitant TLR6 mutation), 1 IRAK1 and 1 TLR5. No mutations were found in IRAK2 and IRAK4. TLR/MYD88-mutated CLL cells overexpressed genes of the NFkB pathway. Patients with TLR/MYD88 mutations were significantly younger (83% ≤50 years) than unmutated, with this being the most frequent mutation in this subgroup of patients. Mutated TLR/MYD88 CLL had higher frequency of mutated IGHV and low expression of CD38 or ZAP-70. Overall survival (OS) was better in TLR/MYD88 mutated than unmutated in the whole series (10-year OS: 100% vs. 62%; p=0.002), and in the subset of patients ≤50 years (100% vs. 70%; p=0.02). In addition, relative OS of TLR/MYD88 mutated patients was similar to age- and gender-matched population. In summary, TLR/MYD88 mutations identify a population of young CLL patients with favorable outcome.
Blood 2014