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.

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.