Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers

Abstract Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare “hairy” B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the...

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Autores principales:	Rachel M. Koldej, Ashvind Prabahran, Chin Wee Tan, Ashley P. Ng, Melissa J. Davis, David S. Ritchie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aae490569fd64e0cb55a0a2f7e4b5132
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spelling	oai:doaj.org-article:aae490569fd64e0cb55a0a2f7e4b51322021-12-02T18:48:23ZDissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers10.1038/s41598-021-98536-12045-2322https://doaj.org/article/aae490569fd64e0cb55a0a2f7e4b51322021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98536-1https://doaj.org/toc/2045-2322Abstract Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare “hairy” B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the BM tumour microenvironment would identify prognostic biomarkers of response to CDA. HCL BM immunology pre and post CDA treatment and healthy controls were analysed using Digital Spatial Profiling to assess the expression of 57 proteins using an immunology panel. A bioinformatics pipeline was developed to accommodate the more complex experimental design of a spatially resolved study. Treatment with CDA was associated with the reduction in expression of HCL tumour markers (CD20, CD11c) and increased expression of myeloid markers (CD14, CD68, CD66b, ARG1). Expression of HLA-DR, STING, CTLA4, VISTA, OX40L were dysregulated pre- and post-CDA. Duration of response to treatment was associated with greater reduction in tumour burden and infiltration by CD8 T cells into the BM post-CDA. This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation and identify biomarkers of response to CDA. With validation in future studies, prospective application of these biomarkers could allow early identification and increased monitoring in patients at increased relapse risk post CDA.Rachel M. KoldejAshvind PrabahranChin Wee TanAshley P. NgMelissa J. DavisDavid S. RitchieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rachel M. Koldej Ashvind Prabahran Chin Wee Tan Ashley P. Ng Melissa J. Davis David S. Ritchie Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
description	Abstract Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare “hairy” B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the BM tumour microenvironment would identify prognostic biomarkers of response to CDA. HCL BM immunology pre and post CDA treatment and healthy controls were analysed using Digital Spatial Profiling to assess the expression of 57 proteins using an immunology panel. A bioinformatics pipeline was developed to accommodate the more complex experimental design of a spatially resolved study. Treatment with CDA was associated with the reduction in expression of HCL tumour markers (CD20, CD11c) and increased expression of myeloid markers (CD14, CD68, CD66b, ARG1). Expression of HLA-DR, STING, CTLA4, VISTA, OX40L were dysregulated pre- and post-CDA. Duration of response to treatment was associated with greater reduction in tumour burden and infiltration by CD8 T cells into the BM post-CDA. This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation and identify biomarkers of response to CDA. With validation in future studies, prospective application of these biomarkers could allow early identification and increased monitoring in patients at increased relapse risk post CDA.
format	article
author	Rachel M. Koldej Ashvind Prabahran Chin Wee Tan Ashley P. Ng Melissa J. Davis David S. Ritchie
author_facet	Rachel M. Koldej Ashvind Prabahran Chin Wee Tan Ashley P. Ng Melissa J. Davis David S. Ritchie
author_sort	Rachel M. Koldej
title	Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
title_short	Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
title_full	Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
title_fullStr	Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
title_full_unstemmed	Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
title_sort	dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aae490569fd64e0cb55a0a2f7e4b5132
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Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers

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