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


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1046135.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 17


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