SGLT‐2 Inhibitors Are Potent to Suppress Aggressive Transformation From Indolent Type of Adult T‐Cell Leukemia/Lymphoma: Unique Insight Into Therapeutics for Diabetes‐Related Hematological Malignancy

Abstract Introduction We previously reported that sodium‐glucose co‐transporter 2 (SGLT‐2) was ectopically overexpressed in adult T‐cell leukemia (ATL) cells notably in aggressive type but in indolent type, and widely‐used anti‐diabetic SGLT‐2 inhibitors (SGLT‐2i) considerably attenuated proliferation of leukemic cells. Methods We performed retrospective analyses for 10 years to see whether SGLT‐2i would prevent aggressive transformation in patients with indolent type ATL accompanied by diabetes. Nucleosome occupancy in the promotor region of the SGLT‐2 gene was also assessed to explore the possible involvement of epigenetic modification in such an ectopic overexpression. Results In patients of indolent ATL with diabetes, the cumulative progression rate in the non‐SGLT‐2i‐treated group was 71%, while no patients developed aggressive transformation in the SGLT‐2i treated group. ATL cells showed an apparent trend to decrease nucleosome occupancy in the promotor region of the SGLT‐2 gene. Conclusion Our data suggest that SGLT‐2i is advantageous for preventing aggravative transformation in indolent ATL. Trial Registration Authors confirmed that clinical trial registration was not requested for the present study and this manuscript.