2026-06-08T10:22:58Zhttps://repisalud.isciii.es/rest/oai/request

oai: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

00925njm 22002777a 4500 dc 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 author 2024-07-20 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. 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 PIM1 is a potential therapeutic target for the leukemogenic effects mediated by JAK/STAT pathway mutations in T-ALL/LBL