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Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis

Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM/TSP could be affected by the development of...

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Detalles Bibliográficos
Autores principales: Nagasaka, Misako, Yamagishi, Makoto, Yagishita, Naoko, Araya, Natsumi, Kobayashi, Seiichiro, Makiyama, Junya, Kubokawa, Miyuki, Yamauchi, Junji, Hasegawa, Daisuke, Coler-Reilly, Ariella L. G., Tsutsumi, Shuntaro, Uemura, Yu, Arai, Ayako, Takata, Ayako, Inoue, Eisuke, Hasegawa, Yasuhiro, Watanabe, Toshiki, Suzuki, Yutaka, Uchimaru, Kaoru, Sato, Tomoo, Yamano, Yoshihisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260950/
https://www.ncbi.nlm.nih.gov/pubmed/32393644
http://dx.doi.org/10.1073/pnas.1920346117
Descripción
Sumario:Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM/TSP could be affected by the development of ATLL, prospective evidence was lacking in this area. In this 5-y prospective cohort study, we determined the mortality, prevalence, and incidence of ATLL in 527 HAM/TSP patients. The standard mortality ratio of HAM/TSP patients was 2.25, and ATLL was one of the major causes of death (5/33 deaths). ATLL prevalence and incidence in these patients were 3.0% and 3.81 per 1,000 person-y, respectively. To identify patients at a high risk of developing ATLL, flow cytometry, Southern blotting, and targeted sequencing data were analyzed in a separate cohort of 218 HAM/TSP patients. In 17% of the HAM/TSP patients, we identified an increase in T cells positive for cell adhesion molecule 1 (CADM1), a marker for ATLL and HTLV-1–infected cells. Genomic analysis revealed that somatic mutations of HTLV-1–infected cells were seen in 90% of these cases and 11% of them had dominant clone and developed ATLL in the longitudinal observation. In this study, we were able to demonstrate the increased mortality in patients with HAM/TSP and a significant effect of ATLL on their prognosis. Having dominant clonal expansion of HTLV-1–infected cells with ATLL-associated somatic mutations may be important characteristics of patients with HAM/TSP who are at an increased risk of developing ATLL.