Pharmacological GLUT3 salvage augments the efficacy of vitamin C-induced TET2 restoration in acute myeloid leukemia.
Jun LiuSuji MinDongchan KimJihyun ParkEunchae ParkShanshan PeiYoungil KohDong-Yeop ShinJa Min ByunMyunggon KoSung Soo YoonJunshik HongPublished in: Leukemia (2023)
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.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- induced apoptosis
- poor prognosis
- signaling pathway
- bone marrow
- hematopoietic stem cell
- cell death
- diabetic rats
- metabolic syndrome
- blood pressure
- risk assessment
- replacement therapy
- acute lymphoblastic leukemia
- long non coding rna
- combination therapy
- climate change