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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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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 |
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author | 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 |
author_facet | 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 |
author_sort | Nagasaka, Misako |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7260950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-72609502020-06-08 Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis 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 Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-05-26 2020-05-11 /pmc/articles/PMC7260950/ /pubmed/32393644 http://dx.doi.org/10.1073/pnas.1920346117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences 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 Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis |
title | Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis |
title_full | Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis |
title_fullStr | Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis |
title_full_unstemmed | Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis |
title_short | Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1–associated myelopathy/tropical spastic paraparesis |
title_sort | mortality and risk of progression to adult t cell leukemia/lymphoma in htlv-1–associated myelopathy/tropical spastic paraparesis |
topic | Biological Sciences |
url | 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 |
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