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

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

doi:10.1111/bjh.18302

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

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

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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.

Original language	English
Pages (from-to)	1011-1015
Number of pages	5
Journal	British Journal of Haematology
Volume	198
Issue number	6
Early online date	8 Jul 2022
DOIs	https://doi.org/10.1111/bjh.18302
Publication status	Published - Sept 2022

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10.1111/bjh.18302Licence: CC BY-NC-ND

Br J Haematol - 2022 - Harrington - Chronic myeloid leukaemia patients at diagnosis and resistant to tyrosine kinaseFinal published version, 929 KBLicence: CC BY-NC-ND

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Harrington, P., Dillon, R., Radia, D., McLornan, D., Woodley, C., Asirvatham, S., Raj, K., Curto-Garcia, N., Saunders, J., Kordasti, S., Harrison, C., & de Lavallade, H. (2022). Chronic myeloid leukaemia patients at diagnosis and resistant to tyrosine kinase inhibitor therapy display exhausted T-cell phenotype. British Journal of Haematology, 198(6), 1011-1015. https://doi.org/10.1111/bjh.18302

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

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.",

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

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: {\textcopyright} 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.",

year = "2022",

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Harrington, P , Dillon, R, Radia, D, McLornan, D, Woodley, C, Asirvatham, S, Raj, K, Curto-Garcia, N, Saunders, J, Kordasti, S , Harrison, C & de Lavallade, H 2022, 'Chronic myeloid leukaemia patients at diagnosis and resistant to tyrosine kinase inhibitor therapy display exhausted T-cell phenotype', British Journal of Haematology, vol. 198, no. 6, pp. 1011-1015. https://doi.org/10.1111/bjh.18302

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AU - Woodley, Claire

AU - Asirvatham, Susan

AU - Raj, Kavita

AU - Curto-Garcia, Natalia

AU - Saunders, Jamie

AU - Kordasti, Shahram

AU - Harrison, Claire

AU - de Lavallade, Hugues

N1 - 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.

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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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JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 6

ER -

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

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