Accession Number:

AD1046135

Title:

Inflammation as a Driver of Clonal Evolution in Myeloproliferative Neoplasm

Descriptive Note:

Technical Report,15 Sep 2016,14 Sep 2017

Corporate Author:

University of California, Irvine Irvine United States

Personal Author(s):

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

Report Date:

2017-10-01

Pagination or Media Count:

17.0

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.

Descriptors:

• neoplasms
• inflammation
• CYTOKINES
• monocytes
• drugs
• inhibitors
• ANTIOXIDANTS

Subject Categories:

• Medicine and Medical Research
• Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE