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Blood. 2014 Jun 12;123(24):3790-6. doi: 10.1182/blood-2013-12-543306. Epub 2014 Apr 29.

Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome.

Author information

1
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and.
2
Unitat de Genòmica, IDIBAPS, Barcelona, Spain;
3
Servei d'Inmunologia, and.
4
Servei d'Hematologia, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain;
5
Servicio de Hematología, Hospital Clínico Universitario, Instituto de Biología molecular y celular del Cancer de Salamanca, Instituto de investigación Biomédica de Salamanca, Centro de Investigación del Cancer, Universidad de Salamanca, Salamanca, Spain;
6
Servicio de Hematología, Hospital Universitario Central de Asturias, Asturias, Spain;
7
Servicio de Hematología, Hospital Clínico de Valencia, Valencia, Spain;
8
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Asturias, Spain;
9
Josep Carreras Leukemia Research Institute, Barcelona, Spain; and.
10
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and Universitat de Barcelona, Barcelona, Spain.

Abstract

Mutations in Toll-like receptor (TLR) and myeloid differentiation primary response 88 (MYD88) genes have been found in chronic lymphocytic leukemia (CLL) at low frequency. We analyzed the incidence, clinicobiological characteristics, and outcome of patients with TLR/MYD88 mutations in 587 CLL patients. 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 overexpressed genes of the nuclear factor κB pathway. Patients with TLR/MYD88 mutations were significantly younger (83% age ≤50 years) than those with no mutations. TLR/MYD88 mutations were the most frequent in young patients. Patients with mutated TLR/MYD88 CLL had a higher frequency of mutated IGHV and low expression of CD38 and ZAP-70. Overall survival (OS) was better in TLR/MYD88-mutated than unmutated patients in the whole series (10-year OS, 100% vs 62%; P = .002), and in the subset of patients age ≤50 years (100% vs 70%; P = .02). In addition, relative OS of TLR/MYD88-mutated patients was similar to that in the age- and gender-matched population. In summary, TLR/MYD88 mutations identify a population of young CLL patients with favorable outcome.

PMID:
24782504
DOI:
10.1182/blood-2013-12-543306
[Indexed for MEDLINE]
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