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Genomic landscape of young ATLL patients identifies frequent targetable CD28 fusions by Noriaki Yoshida; Kay Shigemori; Nicholas Donaldson; Christopher Trevisani; Nicolas A. Cordero; Kristen E. Stevenson; Xia Bu; Fumiko Arakawa; Mai Takeuchi; Koichi Ohshima; Akinori Yoda; Samuel Y. Ng; David M. Weinstock is a Medicine article available to read on EtoBox.

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## Abstract Adult T-cell leukemia/lymphoma (ATLL) in Japan presents at a median age of 70 years and only 5% of patients are <50 years of age. We conducted RNA and targeted DNA sequencing of 8 ATLLs from Japanese patients <50 years of age and identified 3 (37.5%) with both CTLA4-CD28 and inducible costimulator (ICOS)-CD28 fusions. Mutations of PLCG1, PRKCB, and STAT3, which were frequent in other ATLL-sequencing studies, were not identified. Differential expression analysis identified the negative checkpoint molecule LAG3 as the most downregulated gene among cases with the fusions. Immunohistochemistry demonstrated expression of CD80 and CD86, the ligands for CTLA4 and CD28, on ATLL cells and tumor-associated macrophages, respectively. Expression of CTLA4-CD28 in Ba/F3 cells conferred cytokine-independent growth when cocultured with Raji cells that express CD80 and CD86. Growth was associated with recruitment of the p85 subunit of phosphatidylinositol 3-kinase to CTLA4-CD28 and phosphorylation of AKT and extracellular signal-regulated kinase. A CTLA4-blocking antibody reduced cytokine-independent growth in a dose-dependent manner. Together, these results suggest that young Japanese

Who reads Genomic landscape of young ATLL patients identifies frequent targetable CD28 fusions?

Author

Noriaki Yoshida; Kay Shigemori; Nicholas Donaldson; Christopher Trevisani; Nicolas A. Cordero; Kristen E. Stevenson; Xia Bu; Fumiko Arakawa; Mai Takeuchi; Koichi Ohshima; Akinori Yoda; Samuel Y. Ng; David M. Weinstock

Publisher

American Society of Hematology (ISSN 0006-4971)

Published

2020

Language

EN

Field

Medicine (Health Sciences)