Leukemia. 2023;37(8):1638-1648.
Pharmacological GLUT3 salvage augments the efficacy of vitamin C-induced TET2 restoration in acute myeloid leukemia.
제1저자 리우준 · 교신저자 홍준식
소속 (10)
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Center for Medical Innovation, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Biomedical Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
- School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. hongjblood@snu.ac.kr.
- Center for Medical Innovation, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. hongjblood@snu.ac.kr.
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. hongjblood@snu.ac.kr.
- Biomedical Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. hongjblood@snu.ac.kr.
Abstract
Vitamin C has been demonstrated to regulate hematopoietic stem cell frequencies and leukemogenesis by augmenting and restoring Ten-Eleven Translocation-2 (TET2) function, potentially acting as a promising adjunctive therapeutic agent for leukemia. However, glucose transporter 3 (GLUT3) deficiency in acute myeloid leukemia (AML) impedes vitamin C uptake and abolishes the clinical benefit of vitamin C. In this study, we aimed to investigate the therapeutic value of GLUT3 restoration in AML. In vitro GLUT3 restoration was conducted with the transduction of GLUT3-overexpressing lentivirus or the pharmacological salvage with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) treatment to OCI-AML3, a naturally GLUT3-deficient AML cell line. The effects of GLUT3 salvage were further confirmed in patient-derived primary AML cells. Upregulation of GLUT3 expression made AML cells successfully augment TET2 activity and enhanced the vitamin C-induced anti-leukemic effect. Pharmacological GLUT3 salvage has the potential to overcome GLUT3 deficiency in AML and improves the antileukemic effect of vitamin C treatments.
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, Non-U.S. Gov't
- 저널
- Leukemia · eISSN 1476-5551
- 전자 출판
- 2023-07-01
- MeSH
- Humans · Ascorbic Acid / pharmacology · Glucose Transporter Type 3 · Leukemia, Myeloid, Acute* / genetics · Vitamin A / metabolism / therapeutic use / analogs & derivatives · Translocation, Genetic · DNA-Binding Proteins / genetics / metabolism · Dioxygenases* / metabolism
- Substances
- Ascorbic Acid · Glucose Transporter Type 3 · vitamin A2 · Vitamin A · TET2 protein, human · DNA-Binding Proteins · Dioxygenases
- 참고문헌
- 32편