American Society of Hematology, Blood, 24(123), p. 3790-3796, 2014
DOI: 10.1182/blood-2013-12-543306
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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.