Hurtado Navarro, LauraCuenca Zamora, Ernesto JoséZamora, LurdesBellosillo, BeatrizSuch, EsperanzaSoler Espejo, EvaMartínez Banaclocha, HeliosHernández Rivas, Jesús M.Marco Ayala, JavierMartínez Alarcón, LauraLinares Latorre, LolaGarcía Ávila, SaraAmat Martínez, PaulaGonzález, TeresaArnan, MontserratPomares Marín, HelenaCarreño Tarragona, GonzaloChen Liang, Tzu HuaHerranz, María T.García Palenciano, CarlosMorales, María LuzJerez, AndrésLozano, María L.Teruel Montoya, RaúlPelegrín, PabloFerrer Marín, Francisca2024-02-222024-02-222023-12-192666-3791https://hdl.handle.net/2445/207941Chronic 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)-1(3 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-1(3 release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D 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.17 p.application/pdfengcc by-nc-nd (c) Hurtado Navarro, Laura et al., 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/LeucèmiaCitocinesLeukemiaCytokinesinfo:eu-repo/semantics/article2024-02-19info:eu-repo/semantics/openAccess38118408