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dc.contributor.authorWu, Fangtian
dc.contributor.authorWatanabe, Natsuko
dc.contributor.authorTzioni, Maria-Myrsini
dc.contributor.authorAkarca, Ayse
dc.contributor.authorZhang, Chunye
dc.contributor.authorLi, Yan
dc.contributor.authorChen, Zi
dc.contributor.authorCucco, Francesco
dc.contributor.authorCarmell, Natasha
dc.contributor.authorNoh, Jaeduk Yoshimura
dc.contributor.authorIto, Koichi
dc.contributor.authorDobson, Rachel
dc.contributor.authorMoody, Sarah
dc.contributor.authorYao, Wenqing
dc.contributor.authorZhang, Wenyan
dc.contributor.authorLiu, Weiping
dc.contributor.authorLiu, Hongxiang
dc.contributor.authorOkosun, Jessica
dc.contributor.authorChott, Andreas
dc.contributor.authorBi, Yingwen
dc.contributor.authorChuang, Shih-Sung
dc.contributor.authorRaderer, Markus
dc.contributor.authorLi, Jian-Yong
dc.contributor.authorMarafioti, Teresa
dc.contributor.authorDu, Ming-Qing
dc.date.accessioned2021-12-15T11:11:32Z
dc.date.available2021-12-15T11:11:32Z
dc.date.issued2021-12
dc.date.submitted2021-01-31
dc.identifier.issn0887-6924
dc.identifier.others41375-021-01289-z
dc.identifier.other1289
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331476
dc.descriptionFunder: CUH | Addenbrooke’s Charitable Trust, Cambridge University Hospitals (Addenbrooke’s Charitable Trust, Cambridge University Hospitals NHS Foundation Trust); doi: https://doi.org/10.13039/501100002927
dc.descriptionFunder: Pathological Society of Great Britain and Ireland; doi: https://doi.org/10.13039/501100000672
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.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/692/699/67/1990/291/1621/1915
dc.subject/631/67/68
dc.subject/14/63
dc.subject/82/51
dc.subject/14/32
dc.subjectarticle
dc.titleThyroid MALT lymphoma: self-harm to gain potential T-cell help.
dc.typeArticle
dc.date.updated2021-12-15T11:11:31Z
prism.endingPage3508
prism.issueIdentifier12
prism.publicationNameLeukemia
prism.startingPage3497
prism.volume35
dc.identifier.doi10.17863/CAM.78930
dcterms.dateAccepted2021-05-06
rioxxterms.versionofrecord10.1038/s41375-021-01289-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
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
pubs.funder-project-idBloodwise (15019)
cam.issuedOnline2021-05-21


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