Bibliographic Details
| Title: |
Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis. |
| Authors: |
Misako Nagasaka, Makoto Yamagishi, Naoko Yagishita, Natsumi Araya, Seiichiro Kobayashi, Junya Makiyama, Miyuki Kubokawa, Junji Yamauchi, Daisuke Hasegawa, Coler-Reilly, Ariella L. G., Shuntaro Tsutsumi, Yu Uemura, Ayako Arai, Ayako Takata, Eisuke Inoue, Yasuhiro Hasegawa, Toshiki Watanabe, Yutaka Suzuki, Kaoru Uchimaru, Tomoo Sato |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America; 5/26/2020, Vol. 117 Issue 21, p1-7, 7p |
| Subject Terms: |
HTLV, T cells, CELL adhesion molecules, PARAPARESIS |
| Abstract: |
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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
