サカモト　ユウマ   Yuma Sakamoto   坂本　祐真    所属   川崎医科大学  医学部 基礎医学　免疫学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Clinical significance of CD28 gene-related activating alterations in adult T-cell leukaemia/lymphoma.
掲載誌名	正式名：British journal of haematology 略　 称：Br J Haematol ISSNコード：13652141/00071048
掲載区分	国外
巻・号・頁	192(2),pp.281-291
著者・共著者	Yuma Sakamoto, Takashi Ishida, Ayako Masaki, Morishige Takeshita, Hiromi Iwasaki, Kentaro Yonekura, Yukie Tashiro, Asahi Ito, Shigeru Kusumoto, Atae Utsunomiya, Shinsuke Iida, Ryuzo Ueda, Hiroshi Inagaki
発行年月	2021/01
概要	Multiple oncogenic events are involved in the development of adult T-cell leukaemia/lymphoma (ATL). Because CD28 plays a pivotal role in T-cell activation, we focused on alterations of the CD28 gene in ATL. We found multiple genetic abnormalities related to CD28 among the 144 patients enrolled in the present study. These involved gene fusions with the cytotoxic T-lymphocyte-associated antigen 4 or the inducible T-cell co-stimulator in 14 patients (10%), CD28-activating mutations in 3 (2%), and CD28 copy number variations in 34 (24%). Patients with such CD28 gene alterations were significantly younger than those without. In patients not receiving allogeneic haematopoietic stem cell transplantation, those with CD28 gene alterations tended to have a worse prognosis than those without. Finally, patients with chronic or smouldering ATL subtypes with CD28 gene alterations had a significantly worse prognosis than those without. These findings indicate that ATL, especially chronic or smouldering subtypes, have a more aggressive clinical course and are more refractory to conventional chemotherapies or mogamulizumab if they harbour CD28 gene alterations, likely because of continuous, prolonged, and enhanced CD28 activatory signalling. Novel treatment strategies to overcome the effects of these CD28 gene alterations are warranted.
DOI	10.1111/bjh.17211
PMID	33205842