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

• Published in: Scientific reports Vol. 11; no. 1; p. 19056
• Main Authors: Koldej, Rachel M., Prabahran, Ashvind, Tan, Chin Wee, Ng, Ashley P., Davis, Melissa J., Ritchie, David S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.09.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/48; 631/1647/664/1257; 692/308/53/2422; 692/308/575; 692/4028/67/1990; 692/4028/67/327; 692/4028/67/580; Adult; Bioinformatics; Biomarkers; Biomarkers, Tumor - metabolism; Bone marrow; Case-Control Studies; CD11c antigen; CD14 antigen; CD20 antigen; CD8 antigen; Cladribine; CTLA-4 protein; Experimental design; Female; Histocompatibility antigen HLA; Humanities and Social Sciences; Humans; Immunology; Infiltration; Leukemia; Leukemia, Hairy Cell - immunology; Leukemia, Hairy Cell - metabolism; Leukemia, Hairy Cell - pathology; Lymphocytes B; Lymphocytes T; Major Histocompatibility Complex - immunology; Male; Malignancy; Metastases; Microenvironments; Middle Aged; multidisciplinary; Ox40L protein; Prognosis; Science; Science (multidisciplinary); Spatial analysis; Tumor Microenvironment; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-98536-1

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.