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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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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
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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.
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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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