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2023-12-19

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cc by-nc-nd (c) Hurtado Navarro, Laura et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/207941

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

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https://doi.org/10.1016/j.xcrm.2023.101329

Resum

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.

Matèries

Leucèmia, Citocines

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Leukemia, Cytokines

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

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. NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy. _Cell Reports Medicine_. 2023. Vol. 4, núm. 12. [consulta: 13 de gener de 2026]. ISSN: 2666-3791. [Disponible a: https://hdl.handle.net/2445/207941]

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