Authors
Ayako Kamiunten, Daisuke Morishita, Takuro Kameda, Midori Sugiyama, Shunsuke Ebara, Yasunori Kogure, Akio Mizutani, Takaharu Hirayama, Tomohiro Kawamoto, Yotaro Ochi, Kotaro Shide, Hidekazu Tokuhara, Toshio Tanaka, Hiroshi Banno, Yasuyoshi Arikawa, Takamitsu Maru, Hideyuki Oki, Akinori Yoda, Yuki Tahira, Ryoma Ikeda, Kengo Matsumoto, Masayoshi Karasawa, Keiichi Akizuki, Masaaki Sekine, Haruko Shimoda, Tomonori Hidaka, Yoko Kubuki, Hideki Yamaguchi, Hiroo Hasegawa, Yoshitaka Imaizumi, Jun-Ichirou Yasunaga, Masao Matsuoka, Makoto Yoshimitsu, Kenji Ishitsuka, Keisuke Kataoka, Seishi Ogawa, Kazuya Shimoda
Published in
iScience. Volume 29. Issue 8. Pages 116850. Aug 21, 2026. Epub Jul 23, 2026.
Abstract
Adult T cell leukemia/lymphoma (ATL) is an aggressive T cell malignancy with poor prognosis. Recurrent genetic alterations in T cell receptor (TCR) signaling components, including PLCG1, PRKCB, and CARD11, highlight the biological relevance of this pathway in ATL. We focused on mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), a key regulator of TCR signaling that functions through complex formation with CARD11 and BCL10, and developed a potent and selective MALT1 protease inhibitor, CRD-1441551. CRD-1441551 exhibited variable antitumor effects across ATL models both in vitro and in vivo. Among three ATL cell lines and five patient-derived xenograft models, two demonstrated marked sensitivity, three showed modest responses, and three were unresponsive. Notably, therapeutic responses were more frequently observed in models with constitutive MALT1 activation accompanied by enhanced MALT1-NF-κB signaling. These findings suggest that CRD-1441551 preferentially targets a subset of ATL, in which tumor growth is dependent on the MALT1-driven NF-κB pathway.
PMID:
42542590
Bibliographic data and abstract were imported from PubMed on 02 Aug 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 6
- Comments 0