2026-06-08T13:40:14Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/935862024-04-04T17:57:43Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Arenas Cortés, Alicia author Ayala Díaz, Rosa María author Hernández-Campo, Pilar author Gorrochategui, Julián author Primo Niembro, Daniel Arturo author Robles, Alicia author Morales, María Luz author Ballesteros, Joan author Rapado, Inmaculada author Gallardo, Miguel author Linares Gómez, María author Martínez López, Joaquín 2024-01-17T11:53:57Z 2024-01-17T11:53:57Z 2019-05 0390-6078 10.3324/haematol.2018.201038 https://hdl.handle.net/20.500.14352/93586 1592-8721 https://www.haematologica.org/article/view/8896 Ruxolitinib is the front-line non-palliative treatment for myelofibrosis (MF). However, a significant number of patients lose or present suboptimal response, are resistant or have unacceptable toxicity. In an attempt to improve response and avoid the adverse effects of this drug, we evaluated the combination of 17 drugs with ruxolitinib in ex vivo models of peripheral blood mononuclear cells from MF patients and cell lines. We found that the combination ruxolitinib and nilotinib had a synergistic effect against MF cells (ΔEC50 nilotinib, −21.6%). Moreover, the addition of prednisone to combined ruxolitinib/nilotinib improved the synergistic effect in all MF samples studied. We evaluated the molecular mechanisms of combined ruxolitinib/nilotinib/prednisone and observed inhibition of JAK/STAT (STAT5, 69.2+11.8% inhibition) and MAPK (ERK, 29.4+4.5% inhibition) signaling pathways. Furthermore, we found that the triple therapy combination inhibited collagen protein and COL1A1 gene expression in human bone marrow mesenchymal cells. Taken together, we provide evidence that combined ruxolitinib/nilotinib/prednisone is a potential therapy for MF, possibly through the anti-fibrotic effect of nilotinib, the immunomodulatory effect of ruxolitinib and prednisone, and the anti-proliferative effect of ruxolitinib. This combination will be further investigated in a phase Ib/II clinical trial in MF. eng Attribution-NonCommercial 4.0 International Ruxolitinib in combination with prednisone and nilotinib exhibit synergistic effects in human cells lines and primary cells from myeloproliferative neoplasms journal article 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