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NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

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dc.contributor.authorHurtado-Navarro, Laura
dc.contributor.authorCuenca-Zamora, Ernesto J
dc.contributor.authorZamora, Lurdes
dc.contributor.authorBellosillo, Beatriz
dc.contributor.authorSuch, Esperanza
dc.contributor.authorSoler-Espejo, Eva
dc.contributor.authorMartínez-Banaclocha, Helios
dc.contributor.authorHernández-Rivas, Jesus M.
dc.contributor.authorMarco-Ayala, Javier
dc.contributor.authorMartínez-Alarcón, Laura
dc.contributor.authorLinares-Latorre, Lola
dc.contributor.authorGarcía-Ávila, Sara
dc.contributor.authorAmat-Martínez, Paula
dc.contributor.authorGonzález, Teresa
dc.contributor.authorArnan, Monserrat
dc.contributor.authorPomares-Marín, Helena
dc.contributor.authorCarreño-Tarragona, Gonzalo
dc.contributor.authorChen-Liang, Tzu Hua
dc.contributor.authorHerranz, Maria T.
dc.contributor.authorGarcía-Palenciano, Carlos
dc.contributor.authorMorales, María Luz
dc.contributor.authorJerez, Andrés
dc.contributor.authorLozano, Maria L.
dc.contributor.authorTeruel-Montoya, Raul
dc.contributor.authorFerrer-Marín, Francisca
dc.contributor.authorPelegrín Vivancos, Pablo
dc.contributor.departmentBioquímica y Biología Molecular B e Inmunología
dc.date.accessioned2025-01-20T12:52:38Z
dc.date.available2025-01-20T12:52:38Z
dc.date.issued2023-12-19
dc.description© 2023 The Authors. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in Cell Reports Medicine. To access the final edited and published work see https://doi.org/10.1016/j.xcrm.2023.101329es
dc.description.abstractChronic 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 cells 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)-1β 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-1β 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 inhibit NLRP3 inflammasome activation, reduce monocyte count, and improve 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.es
dc.formatapplication/pdfes
dc.format.extent54es
dc.identifier.citationCell Reports Medicine, 2023, Vol. 4, Issue 12 : 101329
dc.identifier.doihttps://doi.org/10.1016/j.xcrm.2023.101329
dc.identifier.issnElectronic: 2666-3791
dc.identifier.urihttp://hdl.handle.net/10201/148841
dc.languageenges
dc.publisherCell Presses
dc.relationOrganismo: MCIN/AEI/10.13039/501100011033. Convocatoria: Proyecto de investigación generación conocimiento. Código: PID2020-116709RB-I00. Organismo: Fundación Séneca. Convocatoria: Proyecto de investigación. Códigos: 20859/PI/18, 21897/PI/22, 21081/PDC/19. Organismo: Instituto de Salud Carlos III. Convocatoria: Proyectos de desarrollo tecnológico. Código: DTS21/00080. Organismo: Instituto de Salud Carlos III. Convocatoria: Proyectos de cooperación internacional. Código: AC22/00009. Organismo: EU Horizon 2020. Convocatoria: Proyectos colaborativos. Código: 96519.es
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2666379123005463es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectLeukemiaes
dc.subjectInflammationes
dc.subjectKRASes
dc.subjectNLRP3 inflammasomees
dc.subjectAnakinraes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.4 - Patología del sistema linfático, órganos hematopoyéticos, endocrinoses
dc.titleNLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapyes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
relation.isAuthorOfPublication.latestForDiscovery547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
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