Morichika Kazuho, Tamaki Keita, Fukushima Takuya, Masuzaki Hiroaki
Division of Endocrinology Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine Graduate School of Medicine University of the Ryukyus Ryukyus Japan.
Laboratory of Immunohematology School of Health Sciences Faculty of Medicine University of the Ryukyus Ryukyus Japan.
EJHaem. 2025 Sep 8;6(5):e70109. doi: 10.1002/jha2.70109. eCollection 2025 Oct.
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.
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 gene was also assessed to explore the possible involvement of epigenetic modification in such an ectopic overexpression.
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 gene.
Our data suggest that SGLT-2i is advantageous for preventing aggravative transformation in indolent ATL.
Authors confirmed that clinical trial registration was not requested for the present study and this manuscript.
我们之前报道过，钠-葡萄糖协同转运蛋白2（SGLT-2）在成人T细胞白血病（ATL）细胞中异位过表达，尤其是在侵袭性类型而非惰性类型中，并且广泛使用的抗糖尿病SGLT-2抑制剂（SGLT-2i）可显著减弱白血病细胞的增殖。
我们进行了为期10年的回顾性分析，以观察SGLT-2i是否能预防伴有糖尿病的惰性型ATL患者发生侵袭性转化。我们还评估了该基因启动子区域的核小体占有率，以探讨表观遗传修饰在这种异位过表达中可能发挥的作用。
在患有糖尿病的惰性ATL患者中，未接受SGLT-2i治疗组的累积进展率为71%，而接受SGLT-2i治疗组中没有患者发生侵袭性转化。ATL细胞在该基因启动子区域的核小体占有率呈现出明显的下降趋势。
我们的数据表明，SGLT-2i有利于预防惰性ATL的病情加重转化。
作者确认本研究及本稿件无需进行临床试验注册。
