Abstract
Human T cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia/lymphoma (ATL), HTLV-1 associated myelopathy (HAM/TSP), and of a number of inflammatory diseases with an estimated 10–20 million infected individuals worldwide. Despite a number of therapeutic approaches, a cure for ATL is still in its infancy. Conventional chemotherapy has short-term efficacy, particularly in the acute subtype. Allogeneic stem cell transplantation offers long-term disease control to around one third of transplanted patients, but few can reach to transplant. This prompted, over the past recent years, the conduction of a number of clinical trials using novel treatments. Meanwhile, new data have been accumulated on biological and molecular bases of HTLV-1 transforming and infecting activity. These data offer new rational for targeted therapies of ATL. Taking into account the double-face of ATL as an hematologic malignancy as well as a viral infectious disease, this Mini-Review seeks to provide an up-to-date overview of recent efforts in the understanding of the mechanisms involved in already used therapeutic regimens showing promising results, and in selecting novel drug targets for ATL.
Highlights
Human T cell leukemia virus type 1 (HTLV-1) is the first identified human retrovirus endemic in southwestern Japan, the Caribbean islands, inter-tropical Africa, South America, Romania and the Middle East, with an estimated 10–20 million infected individuals worldwide
The results showed that the WRN inhibitors NSC 19630 and NSC 617145 efficiently killed HTLV-1-transformed and patient-derived cells, by inducing cell cycle arrest, downregulation of BCl-2, caspase 3 activation, and apoptosis in a dose-dependent manner, without affecting HTLV1 expression (Moles et al, 2016)
A number of studies suggests to take under consideration the suitability of numerous, known drugs to counteract adult T cell leukemia/lymphoma (ATL)
Summary
Human T cell leukemia virus type 1 (HTLV-1) is the first identified human retrovirus endemic in southwestern Japan, the Caribbean islands, inter-tropical Africa, South America, Romania and the Middle East, with an estimated 10–20 million infected individuals worldwide. HTLV-1 is known to cause adult T cell leukemia/lymphoma (ATL), HTLV-1 associated myelopathy (HAM/TSP), and a number of inflammatory diseases. Detected and isolated from a cutaneous T cell lymphoma almost 40 years ago, HTLV-1 still represents a significant challenge for the scientific community engaged to disclose its oncogenic potential and to identify a focused therapy (Gallo, 2005; Tagaya and Gallo, 2017). HTLV-1 transforms CD4+ lymphocytes in vitro and in vivo, and complex mechanisms control virus spreading, expression of viral proteins and host immune response in infected individuals (Figure 1). ATL patients are often refractory to intensive, conventional chemotherapy regimens. Used regimen are CHOP, CHOEP dose-adjusted EPOCH, and hyper-CVAD, alternating with high-dose methotrexate and cytarabine
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