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.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2017
Accession Number
AD1046135

Entities

People

  • Angela Fleischman
  • Brianna Craver
  • Hew Y. Lai
  • Nitya Mehrotra
  • Sarah Morse
  • Stefan Brooks

Organizations

  • University of California, Irvine

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Blood
  • California
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Cytokines
  • Department Of Defense
  • Diseases And Disorders
  • Inflammation
  • Medical Personnel
  • Monocytes
  • Neoplasms
  • Personal Information Managers
  • Production
  • Professional Development
  • Students

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Oncology (Cancer Research).