Pacritinib prevents inflammation-driven myelofibrosis-like phenotype in a miR-146a-/- murine model
Year: 2024
Type: article
Abstract: mice were treated either with or without pacritinib, for 3 or 6 months. Notably, pacritinib prevented the splenomegaly, reticulin fibrosis and osteosclerosis observed in untreated KO mice. Pacritinib also avoided the myeloproliferation, loss of splenic architecture, and extramedullary hematopoiesis observed in age-matched untreated KO mice. Pharmacological targeting of IRAK1/JAK2 attenuated the pro-inflammatory environment, preventing the increase of inflammatory cytokines, particularly CXCL1 and TNF-α, without inducing cytopenias but rather the opposite. Compared to age-matched untreated KO mice, treated mice showed higher platelet counts irrespective of treatment duration, and higher erythrocyte counts with the longer treatment. Additionally, pacritinib preventive treatment reduced COL1A1 production in an in vitro model mimicking JAK2-driven fibrosis. These findings highlight that dual inhibition of JAK2/IRAK1 with pacritinib, by delaying or attenuating the myelofibrotic progression, could be a potential modifier of the natural course of MPN.
Source: Biomedicine & Pharmacotherapy
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,420
Awards: Identificación de biomarcadores de riesgo trombótico en pacientes con neoplasias mieloproliferativas: un enfoque clínico, biológico y molecular, G4466232843, Identificación de nuevos factores implicados en el inicio, progresión y complicaciones de las Neoplasias Mieloproliferativas Crónicas Philadelphia Negativas, Regulación de la tromboinflamación por microRNA: aproximación biológica y terapéutica en enfermedad cardiovascular post-sepsis, G5725833701, G7346170248
OpenAlex ID: W4404730730