RT Journal Article
T1 Ruxolitinib in combination with prednisone and nilotinib exhibit synergistic effects in human cells lines and primary cells from myeloproliferative neoplasms
A1 Arenas Cortés, Alicia
A1 Ayala Díaz, Rosa María
A1 Hernández-Campo, Pilar
A1 Gorrochategui, Julián
A1 Primo Niembro, Daniel Arturo
A1 Robles, Alicia
A1 Morales, María Luz
A1 Ballesteros, Joan
A1 Rapado, Inmaculada
A1 Gallardo, Miguel
A1 Linares Gómez, María
A1 Martínez López, Joaquín
AB 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.
PB Ferrata Storti Foundation
SN 0390-6078
YR 2019
FD 2019-05
LK https://hdl.handle.net/20.500.14352/93586
UL https://hdl.handle.net/20.500.14352/93586
LA eng
NO Subdirección General de Investigación Sanitaria (Instituto de Salud Carlos III, Spain)
NO CRIS against Cancer foundation
NO Spanish Ministry of Economy and Competitiveness
DS Docta Complutense
RD 6 abr 2025