Show simple item record

dc.contributor.authorØbro, Nina F
dc.contributor.authorGrinfeld, Jacob
dc.contributor.authorBelmonte, Miriam
dc.contributor.authorIrvine, Melissa
dc.contributor.authorShepherd, Mairi
dc.contributor.authorRao, Tata Nageswara
dc.contributor.authorKarow, Axel
dc.contributor.authorRiedel, Lisa M
dc.contributor.authorHarris, Oliva B
dc.contributor.authorBaxter, Joanna
dc.contributor.authorNangalia, Jyoti
dc.contributor.authorGodfrey, Anna
dc.contributor.authorHarrison, Claire N
dc.contributor.authorLi, Juan
dc.contributor.authorSkoda, Radek C
dc.contributor.authorCampbell, Peter J
dc.contributor.authorGreen, Tony
dc.contributor.authorKent, David G
dc.date.accessioned2020-06-02T23:30:25Z
dc.date.available2020-06-02T23:30:25Z
dc.date.issued2020-06
dc.identifier.issn2572-9241
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/306025
dc.description.abstractMyeloproliferative neoplasms (MPNs) are characterized by deregulation of mature blood cell production and increased risk of myelofibrosis (MF) and leukemic transformation. Numerous driver mutations have been identified but substantial disease heterogeneity remains unexplained, implying the involvement of additional as yet unidentified factors. The inflammatory microenvironment has recently attracted attention as a crucial factor in MPN biology, in particular whether inflammatory cytokines and chemokines contribute to disease establishment or progression. Here we present a large-scale study of serum cytokine profiles in more than 400 MPN patients and identify an essential thrombocythemia (ET)-specific inflammatory cytokine signature consisting of Eotaxin, GRO-α, and EGF. Levels of 2 of these markers (GRO-α and EGF) in ET patients were associated with disease transformation in initial sample collection (GRO-α) or longitudinal sampling (EGF). In ET patients with extensive genomic profiling data (n = 183) cytokine levels added significant prognostic value for predicting transformation from ET to MF. Furthermore, CD56+CD14+ pro-inflammatory monocytes were identified as a novel source of increased GRO-α levels. These data implicate the immune cell microenvironment as a significant player in ET disease evolution and illustrate the utility of cytokines as potential biomarkers for reaching beyond genomic classification for disease stratification and monitoring.
dc.description.sponsorshipThe serum cytokine studies were supported by a research grant from the Rosetrees Trust. NFØ was supported by grants from the Danish Lundbeck Foundation and Danish Cancer Society, J.G. was supported by fellowships from Bloodwise and the Kay Kendall Leukaemia Fund; and M.S.S. is the recipient of a Biotechnology and Biological Sciences Research Council Industrial Collaborative Awards in Science and Engineering PhD Studentship. Work in the R.C.S. laboratory was supported by grants from the Stiftung Blutspendezentrum SRK beider Basel, the Swiss National Science Foundation (31003A-147016/1 and 31003A_166613), and the Swiss Cancer League (KLS-2950-02-2012 and KFS-3655-02-2015). A.K. was supported by the Else Kröner-Fresenius Foundation. Work in the A.R.G. laboratory is supported by the Wellcome Trust, Bloodwise, Cancer Research UK, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America. Work in the D.G.K. laboratory is supported by a Bloodwise Bennett Fellowship (15008), a European Hematology Association Non-Clinical Advanced Research Fellowship, and an ERC Starting Grant (ERC-2016-STG–715371). D.G.K. and A.R.G. are supported by a core support grant from the Wellcome Trust and Medical Research Council to the Wellcome MRC Cambridge Stem Cell Institute, the National Institute for Health Research Cambridge Biomedical Research Centre, and the CRUK Cambridge Cancer Centre.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.rightsAll rights reserved
dc.titleLongitudinal Cytokine Profiling Identifies GRO-α and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia.
dc.typeArticle
prism.issueIdentifier3
prism.publicationDate2020
prism.publicationNameHemasphere
prism.startingPagee371
prism.volume4
dc.identifier.doi10.17863/CAM.53106
dcterms.dateAccepted2020-03-09
rioxxterms.versionofrecord10.1097/HS9.0000000000000371
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-06
dc.contributor.orcidShepherd, Mairi [0000-0002-4328-9882]
dc.contributor.orcidBaxter, Joanna [0000-0002-5946-5238]
dc.contributor.orcidNangalia, Jyoti [0000-0001-7122-4608]
dc.contributor.orcidGreen, Tony [0000-0002-9795-0218]
dc.identifier.eissn2572-9241
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idMedical Research Council (MR/M008975/1)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.issuedOnline2020-06
cam.orpheus.successTue Sep 01 14:00:34 BST 2020 - Embargo updated
rioxxterms.freetoread.startdate2021-06-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record