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	Immunohistochemistry for CCR4 C-terminus predicts CCR4 mutations and mogamulizumab efficacy in adult T-cell leukemia/lymphoma.
掲載誌名	正式名：The journal of pathology. Clinical research 略　 称：J Pathol Clin Res ISSNコード：20564538/20564538
掲載区分	国外
巻・号・頁	7(1),pp.52-60
著者・共著者	Keiichiro Fujii, Yuma Sakamoto, Ayako Masaki, Takayuki Murase, Yukie Tashiro, Kentaro Yonekura, Atae Utsunomiya, Asahi Ito, Shigeru Kusumoto, Shinsuke Iida, Ryuzo Ueda, Takashi Ishida, Hiroshi Inagaki
発行年月	2021/01
概要	Mogamulizumab targets extracellular N-terminal domain of CCR4, which is expressed in most adult T-cell leukemia/lymphoma (ATL) cases. Recently, we reported that CCR4 C-terminal gain-of-function mutations were frequent in ATL cases, and a subgroup with these mutations who were treated without allogenic hematopoietic stem cell transplantation (HSCT) and with mogamulizumab-containing [HSCT (-) and mogamulizumab (+)] regimens had a superior survival rate. Although these mutations are most likely a biomarker for predicting a strong response to mogamulizumab, their detection is time-consuming and costly. A more convenient screening tool may be necessary in the clinical setting. In this study, the clinicopathological importance of immunohistochemistry for the CCR4 N-terminus (CCR4-N-IHC) and C-terminus (CCR4-C-IHC) was examined in a large ATL cohort (n = 92). We found that CCR4-C-IHC, but not CCR4-N-IHC, was inversely correlated with the CCR4 mutation status. In ATL patients negative for CCR4-C-IHC, a subgroup treated with HSCT (-) and mogamulizumab (+) regimens showed a significantly better prognosis. In addition, CCR4-C-IHC was found to be a useful marker for high-sensitivity screening of the CCR4 mutational status (87%). The present study suggests that CCR4-C-IHC may be useful for identifying ATL patients harboring mutated CCR4 who may benefit from the superior efficacy of mogamulizumab-containing regimens and that CCR4-C-IHC may be a rapid and cost-efficient tool for screening for CCR4 mutation status.
DOI	10.1002/cjp2.180
PMID	33022137