Inflammation as a Driver of Clonal Evolution in Myeloproliferative Neoplasm
Abstract
Tumor Necrosis Factor-alpha (TNF) is elevated in myeloproliferative neoplasm (MPN) and plays a key role in expansion of the JAK2V617F neoplastic clone. We have found that MPN monocytes produce excessive amounts of TNF in response to TLR ligation due to a defect in the negative regulatory feedback loop which normally serves to dampen TNF production. We have localized this defect to a blunted response to the anti-inflammatory cytokine IL-10. MPN monocytes are less responsive to the anti-inflammatory actions of IL-10 at low concentrations but these effects can be restored by increasing the concentration of IL-10. Together, these data suggest that administration of IL-10 may reduce excessive inflammatory cytokine production in MPN.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1064021
Entities
People
- Angela Fleischman
- Brianna Craver
- Daniel Kim
- Hew Yeng Lai
- Stefan Brooks
Organizations
- University of California, Irvine