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Integrated molecular and immunological features of human T-lymphotropic virus type 1 infection and disease progression to adult T-cell leukaemia or lymphoma

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LANCET HAEMATOLOGY
卷 10, 期 7, 页码 539-548

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ELSEVIER SCI LTD

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The human T-lymphotropic virus type 1 (HTLV-1) retrovirus infects millions of people globally, causing lifelong infection and immune suppression. It is associated with adult T-cell leukaemia or lymphoma (ATLL) in a small percentage of cases, with poor treatment outcomes. Recent advancements have shed light on the genetic, molecular, and immunological events occurring in HTLV-1 infection and ATLL progression. A four-step disease model has been proposed, providing insights into potential biomarkers and therapeutic targets. This model aims to promote research interest and guide the development of effective treatments for this neglected virus and its associated rare cancer.
The human T-lymphotropic virus type 1 (HTLV-1) retrovirus infects 10-20 million people globally, with endemic regions in southwestern Japan, the Caribbean basin, Africa, and central Australia. HTLV-1 is associated with lifelong infection and immune suppression, resulting in a range of serious sequalae, including adult T-cell leukaemia or lymphoma (ATLL) in 5% of cases. To date, there are no preventive or curative treatments for HTLV-1 and treatment outcomes for ATLL remain generally poor. Depending on the disease subtype, overall survival is 8-55 months. Recent advancements in the past decade have identified genetic, molecular, and immunological events occurring throughout the lives of individuals infected with HTLV-1 and of those who progress to ATLL. In addition, updated guidelines for clinical management have been published. With the aim of focusing research efforts on the development of treatments for both HTLV-1 infections and ATLL, we have conceptualised a four-step disease model for HTLV-1-associated ATLL: (1) viral exposure, (2) establishment of chronic infection, (3) cellular transformation and evolution, and (4) disease presentation and management. For each stage we describe the clinical features, molecular and immunological factors involved, potential biomarkers of disease progression, and the therapeutic applicability of individual targets. We also discuss emerging concepts and novel treatment approaches. Our hope is that this model will promote research interest and guide the testing of new treatments for this neglected virus and its associated rare cancer.

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