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dc.contributor.author | Lahera, Antonio | |
dc.contributor.author | Vela-Martín, Laura | |
dc.contributor.author | Fernandez-Navarro, Pablo L | |
dc.contributor.author | Llamas, Pilar | |
dc.contributor.author | López-Lorenzo, José L | |
dc.contributor.author | Cornago, Javier | |
dc.contributor.author | Santos, Javier | |
dc.contributor.author | Fernández-Piqueras, José | |
dc.contributor.author | Villa-Morales, María | |
dc.date.accessioned | 2023-09-26T09:17:35Z | |
dc.date.available | 2023-09-26T09:17:35Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Mol Carcinog. 2024 Jan;63(1):5-10. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16500 | |
dc.description.abstract | T-cell acute lymphoblastic leukemia (T-ALL) arises from the malignant transformation of T-cell progenitors at various differentiation stages. Given that patients who relapse have a dismal prognosis, there is an urgent need to identify the molecular alterations that are present in such patients and promote leukemogenesis to implement personalized therapies with higher efficacy and fewer adverse effects. In the present manuscript, we identified the JAK3Q988P mutation in a T-ALL patient who did not achieve a durable response after the conventional treatment and whose tumor cells at relapse presented constitutive activation of the JAK/STAT pathway. Although JAK3Q988P has been previously identified in T-ALL patients from different studies, the functional consequences exerted by this mutation remain unexplored. Through the combination of different hematopoietic cellular models, we functionally characterize JAK3Q988P as an oncogenic mutation that contributes to leukemogenesis. Notably, JAK3Q988P not only promotes constitutive activation of the JAK/STAT pathway in the absence of cytokines and growth factors, as is the case for other JAK3 mutations that have been functionally characterized as oncogenic, but also functions independently of JAK1 and IL2RG, resulting in high oncogenic potential as well as resistance to ruxolitinib. Our results indicate that ruxolitinib may not be efficient for future patients bearing the JAK3Q988P mutation who instead may obtain greater benefits from treatments involving other pharmacological inhibitors such as tofacitinib. | es_ES |
dc.description.sponsorship | This work was supported in part by funds from Ministerio de Economía y Competitividad (SAF2015‐70561‐R; MINECO/FEDER, EU to J.F.‐P. and M.V.‐M.); Ministerio de Ciencia, Innovación y Universidades (RTI2018‐093330‐B‐I00; MCIU/FEDER, EU to J.F.‐P. and J.S.); Fundación Ramón Areces (CIVP19S7917 to J.F.‐P.); Comunidad de Madrid (B2017/BMD‐3778; LINFOMAS‐CM to J.F.‐P.); Asociación Española Contra el Cáncer (AECC, 2018; PROYE18054PIRI to J.F.‐P.);and Instituto de Investigación Sanitaria Fundación Jiménez Díaz to J.F.‐P.;institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.subject | JAK/STAT | es_ES |
dc.subject | JAK3 | es_ES |
dc.subject | T-ALL | es_ES |
dc.subject | Ruxolitinib | es_ES |
dc.title | The JAK3Q988P mutation reveals oncogenic potential and resistance to ruxolitinib | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Atribución-NoComercial 4.0 Internacional | * |
dc.identifier.pubmedID | 37712558 | es_ES |
dc.identifier.doi | 10.1002/mc.23632 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Fundación Ramón Areces | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Asociación Española Contra el Cáncer | es_ES |
dc.contributor.funder | Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz | es_ES |
dc.contributor.funder | Banco Santander | es_ES |
dc.contributor.funder | Centro de Biología Molecular Severo Ochoa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1098-2744 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1002/mc.23632 | es_ES |
dc.identifier.journal | Molecular carcinogenesis | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Epidemiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2015‐70561‐R | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018‐093330‐B‐I00 | es_ES |