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Chronic myeloid leukaemia patients at diagnosis and resistant to tyrosine kinase inhibitor therapy display exhausted T-cell phenotype

Research output: Contribution to journalArticlepeer-review

Patrick Harrington, Richard Dillon, Deepti Radia, Donal McLornan, Claire Woodley, Susan Asirvatham, Kavita Raj, Natalia Curto-Garcia, Jamie Saunders, Shahram Kordasti, Claire Harrison, Hugues de Lavallade

Original languageEnglish
Pages (from-to)1011-1015
Number of pages5
JournalBritish Journal of Haematology
Volume198
Issue number6
Early online date8 Jul 2022
DOIs
Accepted/In press23 May 2022
E-pub ahead of print8 Jul 2022
PublishedSep 2022

Bibliographical note

Funding Information: Patrick Harrington: Research funding from Bristol Myers Squibb and speaker fees from Incyte. Donal McLornan: Speaker fees and advisory boards from Novartis, Celgene and Jazz pharmaceuticals. Shahram Kordasti: Research grants from Celgene and Novartis; Alexion speaker honorarium. Claire Harrison: Novartis; speaker fees from Novartis, Janssen, CTI, Celgene, Medscape; Advisory Board: Incyte, CTI, Sierra Oncology, Novartis, Celgene, Roche, AOP pharma, Geron and Astra Zenica. Hugues de Lavallade: Grants and speaker fees from Bristol Myers Squibb and Incyte; speaker fees from Novartis and Pfizer. Publisher Copyright: © 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

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Abstract

The search for novel targets in chronic myeloid leukaemia (CML) is ongoing, to improve treatment efficacy in refractory disease and increase eligibility for tyrosine kinase inhibitor (TKI) discontinuation. Increased frequency of Tregs and effector Tregs was evident at diagnosis, together with increased expression of T-cell exhaustion markers, including in regulatory T cells at diagnosis and in patients with refractory disease. Plasma analysis revealed significantly increased levels of cytokines including tumour necrosis factor (TNF)-a and interleukin (IL)-6 at diagnosis, in keeping with a pro-inflammatory state prior to treatment. We hence demonstrate T-cell exhaustion and a pro-inflammatory state at diagnosis in CML, likely secondary to leukaemia-associated antigenic overload associated with increased disease burden.

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