2026-06-08T10:22:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/262572025-12-18T13:00:17Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19608col_20.500.12105_16977
Repisalud
author
Lahera, Antonio
author
Vela-Martín, Laura
author
Fernandez-Navarro, Pablo L
author
Llamas, Pilar
author
López-Lorenzo, José L
author
Cornago, Javier
author
Santos, Javier
author
Fernández-Piqueras, José
author
Villa-Morales, María
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación Ramón Areces
funder
Comunidad de Madrid (España)
funder
Asociación Española Contra el Cáncer
funder
Fundación Banco Santander
funder
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
2025-02-05T08:04:07Z
2025-02-05T08:04:07Z
2024-07-20
Lahera A, Vela-Martín L, Fernández-Navarro P, Llamas P, López-Lorenzo JL, Cornago J, Santos J, Fernández-Piqueras J, Villa-Morales M. PIM1 is a potential therapeutic target for the leukemogenic effects mediated by JAK/STAT pathway mutations in T-ALL/LBL. NPJ Precis Oncol. 2024 Jul 20;8(1):152.
10.1038/s41698-024-00638-2
2397-768X
NPJ precision oncology
39033228
https://hdl.handle.net/20.500.12105/26257
Precursor T-cell neoplasms (T-ALL/LBL) are aggressive hematological malignancies that arise from the malignant transformation of immature thymocytes. Despite the JAK/STAT pathway is recurrently altered in these neoplasms, there are not pharmacological inhibitors officially approved for the treatment of T-ALL/LBL patients that present oncogenic JAK/STAT pathway mutations. In the effort to identify potential therapeutic targets for those patients, we followed an alternative approach and focused on their transcriptional profile. We combined the analysis of molecular data from T-ALL/LBL patients with the generation of hematopoietic cellular models to reveal that JAK/STAT pathway mutations are associated with an aberrant transcriptional profile. Specifically, we demonstrate that JAK/STAT pathway mutations induce the overexpression of the PIM1 gene. Moreover, we show that the pan-PIM inhibitor, PIM447, significantly reduces the leukemogenesis, as well as the aberrant activation of c-MYC and mTOR pathways in cells expressing different JAK/STAT pathway mutations, becoming a potential therapeutic opportunity for a relevant subset of T-ALL/LBL patients.
eng
PIM1 is a potential therapeutic target for the leukemogenic effects mediated by JAK/STAT pathway mutations in T-ALL/LBL
research article
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PIM1_PotentialTherapeuticTarget_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/79533188-f7e8-49ed-b167-db80a33909a8/download
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Supplementary_PIM1_PotentialTherapeuticTarget_2024.pdf