Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome.
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.
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and.
Alejandra
A
Martínez-Trillos
Unitat de Genòmica, IDIBAPS, Barcelona, Spain;
Magda
M
Pinyol
Unitat de Genòmica, IDIBAPS, Barcelona, Spain;
Alba
A
Navarro
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and.
Marta
M
Aymerich
Unitat de Genòmica, IDIBAPS, Barcelona, Spain;
Pedro
P
Jares
Servei d'Inmunologia, and.
Manel
M
Juan
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and.
María
M
Rozman
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and.
Dolors
D
Colomer
Servei d'Hematologia, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain;
Julio
J
Delgado
Servei d'Hematologia, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain;
Eva
E
Giné
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;
Marcos
M
González-Díaz
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;
Jesús M
JM
Hernández-Rivas
Servicio de Hematología, Hospital Universitario Central de Asturias, Asturias, Spain;
Enrique
E
Colado
Servicio de Hematología, Hospital Universitario Central de Asturias, Asturias, Spain;
Consolación
C
Rayón
Servicio de Hematología, Hospital Universitario Central de Asturias, Asturias, Spain;
Angel R
AR
Payer
Servicio de Hematología, Hospital Clínico de Valencia, Valencia, Spain;
Maria José
MJ
Terol
Servicio de Hematología, Hospital Clínico de Valencia, Valencia, Spain;
Blanca
B
Navarro
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Asturias, Spain;
Victor
V
Quesada
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Asturias, Spain;
Xosé S
XS
Puente
Josep Carreras Leukemia Research Institute, Barcelona, Spain; and.
Ciril
C
Rozman
Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Asturias, Spain;
Carlos
C
López-Otín
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.
Elías
E
Campo
Servei d'Hematologia, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain;
Armando
A
López-Guillermo
Unitat d'Hematopatologia, Servei d'Anatomia Patològica, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and.
Neus
N
Villamor
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult
D053594:Myeloid Differentiation Factor 88