Quantification of T cell clonality in Human T cell leukaemia virus type-1 carriers can detect the development of Adult T cell Leukaemia early
| Autor: | Graham P. Taylor, Aileen G. Rowan, Sonia N Wolf, Lucy Cook, Claire Greiller, Jana Haddow |
|---|---|
| Přispěvatelé: | Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC) |
| Rok vydání: | 2021 |
| Předmět: |
Male
Lymphoma Lymphocyte T cell CD3 T-Lymphocytes viruses CCR4 Antigens CD7 Peripheral blood mononuclear cell lcsh:RC254-282 Virus Article immune system diseases hemic and lymphatic diseases medicine Leukaemia Humans Leukemia-Lymphoma Adult T-Cell Tumour virus infections 1112 Oncology and Carcinogenesis Longitudinal Studies 1102 Cardiorespiratory Medicine and Haematology Cells Cultured Early Detection of Cancer Aged Human T-lymphotropic virus 1 biology business.industry T-cell receptor hemic and immune systems Hematology Translational research Middle Aged medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens HTLV-I Infections medicine.anatomical_structure Ki-67 Antigen Oncology Immunology biology.protein Female business |
| Zdroj: | Blood Cancer Journal, Vol 11, Iss 3, Pp 1-11 (2021) Blood Cancer Journal |
| Popis: | Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26− T-cells) using an ‘oligoclonality index’ (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up (n = 38) and patients with ATL (n = 30). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL (n = 106), 19% of high proviral load (PVL, ≥4 copies of HTLV-1/100 PBMCs) carriers had an OCI-flow in the ATL range, >0.770. Carriers with an OCI-flow >0.770 (n = 14) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow ≤0.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow ≤0.770 (p = 0.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|