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Title: | NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy |
Author: | Hurtado Navarro, Laura Cuenca Zamora, Ernesto José Zamora, Lurdes Bellosillo, Beatriz Such, Esperanza Soler Espejo, Eva Martínez Banaclocha, Helios Hernández Rivas, Jesús M. Marco Ayala, Javier Martínez Alarcón, Laura Linares Latorre, Lola García Ávila, Sara Amat Martínez, Paula González, Teresa Arnan, Montserrat Pomares Marín, Helena Carreño Tarragona, Gonzalo Chen Liang, Tzu Hua Herranz, María T. García Palenciano, Carlos Morales, María Luz Jerez, Andrés Lozano, María L. Teruel Montoya, Raúl Pelegrín, Pablo Ferrer Marín, Francisca |
Keywords: | Leucèmia Citocines Leukemia Cytokines |
Issue Date: | 19-Dec-2023 |
Publisher: | Elsevier BV |
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)-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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.xcrm.2023.101329 |
It is part of: | Cell Reports Medicine, 2023, vol. 4, num. 12 |
URI: | http://hdl.handle.net/2445/207941 |
Related resource: | https://doi.org/10.1016/j.xcrm.2023.101329 |
ISSN: | 2666-3791 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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