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dc.contributor.authorWu, Fangtianen
dc.contributor.authorWatanabe, Natsukoen
dc.contributor.authorTzioni, Maria-Myrsinien
dc.contributor.authorAkarca, Ayseen
dc.contributor.authorZhang, Chunyeen
dc.contributor.authorLi, Yanen
dc.contributor.authorChen, Zien
dc.contributor.authorCucco, Francescoen
dc.contributor.authorCarmell, Natashaen
dc.contributor.authorNoh, Jaeduk Yoshimuraen
dc.contributor.authorIto, Koichien
dc.contributor.authorDobson, Rachelen
dc.contributor.authorMoody, Sarahen
dc.contributor.authorYao, Wenqingen
dc.contributor.authorZhang, Wenyanen
dc.contributor.authorLiu, Weipingen
dc.contributor.authorLiu, Hongxiangen
dc.contributor.authorOkosun, Jessicaen
dc.contributor.authorChott, Andreasen
dc.contributor.authorBi, Yingwenen
dc.contributor.authorChuang, Shih-Sungen
dc.contributor.authorRaderer, Markusen
dc.contributor.authorLi, Jian-Yongen
dc.contributor.authorMarafioti, Teresaen
dc.contributor.authorDu, Ming-Qingen
dc.date.accessioned2021-04-30T23:30:29Z
dc.date.available2021-04-30T23:30:29Z
dc.date.issued2021-05-21en
dc.identifier.issn0887-6924
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/321796
dc.description.abstractThe development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2 (86%), CD274 (53%), TNFRSF14 (53%) and TNFAIP3 (30%) in thyroid MALT lymphoma. CD274 was also frequently deleted, together with mutation seen in 68% of cases. There was a significant association between CD274 mutation/deletion and TNFRSF14 mutation (P=0.001). CD274 (PD-L1) and TNFRSF14 are ligands for the co-inhibitory receptor PD1 and BTLA on T-helper cells, respectively, their inactivation may free T-cell activities, promoting their help to malignant B-cells. In support of this, both the proportion of activated T-cells (CD4+CD69+/CD4+) within the proximity of malignant B-cells, and the level of transformed blasts were significantly higher in cases with CD274/TNFRSF14 genetic abnormalities than those without these changes. Both CD274 and TNFRSF14 genetic changes were significantly associated with Hashimoto’s thyroiditis (P=0.01, P=0.04 respectively), and CD274 mutation/deletion additionally associated with increased erythrocyte sedimentation rate (P=0.0001). In conclusion, CD274/TNFRSF14 inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.
dc.description.sponsorshipBloodwise the Kay Kendall Leukaemia Fund the Addenbrooke’s Charitable Trust Pathological Society of Great Britain and Ireland
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature [academic journals on nature.com]
dc.rightsAll rights reserved
dc.rights.uri
dc.titleThyroid MALT lymphoma: self-harm to gain potential T-cell help.en
dc.typeArticle
prism.publicationDate2021en
prism.publicationNameLeukemiaen
dc.identifier.doi10.17863/CAM.69253
dcterms.dateAccepted2021-05-06en
rioxxterms.versionofrecord10.1038/s41375-021-01289-zen
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-05-21en
dc.contributor.orcidAkarca, Ayse [0000-0003-0629-3927]
dc.contributor.orcidMoody, Sarah [0000-0003-4904-1041]
dc.contributor.orcidOkosun, Jessica [0000-0001-6021-5044]
dc.contributor.orcidRaderer, Markus [0000-0002-3248-5802]
dc.contributor.orcidDu, Ming-Qing [0000-0002-1017-5045]
dc.identifier.eissn1476-5551
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBloodwise (15019)
cam.orpheus.successMon May 31 07:30:58 BST 2021 - Embargo updated*
cam.orpheus.counter4*
rioxxterms.freetoread.startdate2021-11-21


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