Portal de investigación
NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Hurtado-Navarro L
- Cuenca-Zamora EJ
- Zamora L
- Bellosillo B
- Soler-Espejo E
- Martínez-Banaclocha H
- Hernández-Rivas JM
- Martínez-Alarcón L
- Linares-Latorre L
- García-Ávila S
- Amat-Martínez P
- Arnan M
- Pomares-Marín H
- Carreño-Tarragona G
- Chen-Liang TH
- Herranz MT
- García-Palenciano C
- Morales ML
- Lozano ML
- Teruel-Montoya R
- Pelegrín P
- Ferrer-Marín F
Grupos
Abstract
Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1ß release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1ß release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRAS(G12D) mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 2666-3791, 2666-3791
- Tipo:
- Article
- Páginas:
- 101329-101329
- PubMed:
- 38118408
- Factor de Impacto:
- 5,956 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
CELL REPORTS MEDICINE Cell Press
Documentos
- No hay documentos
Filiaciones
Keywords
- CMML; IL-1 blockers; KRAS; NLRP3 blockers; NLRP3 inflammasome; RAS mutations; anakinra; inflammation; myelodysplastic syndromes; myeloproliferative neoplasms
Cita
Hurtado L,Cuenca EJ,Zamora L,Bellosillo B,SUCH E,Soler E,Martínez H,Hernández JM,MARCO J,Martínez L,Linares L,García S,Amat P,GONZÁLEZ T,Arnan M,Pomares H,Carreño G,Chen TH,Herranz MT,García C,Morales ML,JEREZ A,Lozano ML,Teruel R,Pelegrín P,Ferrer F. NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy. Cell Rep Med. 2023. 4. (12):p. 101329-101329. IF:11,700. (1).