{"id":"77e5508a-be06-54ef-96a1-d355f5187b1c","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:slc2a3-gates-vitamin-c-tet2-restoration","predicate":"supports","statement":"In patient-derived primary acute-myeloid-leukaemia cells, vitamin C restored TET2 activity only when SLC2A3 was expressed, and SLC2A3 knockdown in the KG-1 cell line decreased the response to vitamin C.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"cb1a62c8-3007-58a6-ab72-ee29f67ec9cd","mechanism_event_label":"In patient-derived primary acute-myeloid-leukaemia cells, vitamin C restored TET2 activity only when SLC2A3 was expressed, and SLC2A3 knockdown in the KG-1 cell line decreased the response to vitamin C.","subject":{"id":"638014a4-29fe-5df4-b9cd-8585768c5c31","slug":"human-slc2a3","display_name":"Human GLUT3 / SLC2A3","entity_type_key":"protein"},"object":{"id":"61186857-2faa-5498-9207-b637a63e4276","slug":"ascorbate-cellular-uptake","display_name":"Cellular ascorbate uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cb1a62c8-3007-58a6-ab72-ee29f67ec9cd","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:slc2a3-gates-vitamin-c-tet2-restoration-event","event_type":"observed_relationship","label":"In patient-derived primary acute-myeloid-leukaemia cells, vitamin C restored TET2 activity only when SLC2A3 was expressed, and SLC2A3 knockdown in the KG-1 cell line decreased the response to vitamin C.","description":"If the cell cannot take vitamin C in, the vitamin cannot restore the enzyme.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"638014a4-29fe-5df4-b9cd-8585768c5c31","slug":"human-slc2a3","display_name":"Human GLUT3 / SLC2A3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"61186857-2faa-5498-9207-b637a63e4276","slug":"ascorbate-cellular-uptake","display_name":"Cellular ascorbate uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"role":"enzyme whose restoration depends on the transporter","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Culture experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"AML cell lines, an SLC2A3-knockdown line and patient-derived primary AML cells; TCGA and TARGET expression analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Vitamin C, with and without SLC2A3 knockdown","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Below-median SLC2A3 expression was associated with poorer overall survival, which is an association within a database cohort and not an experimental outcome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"If the cell cannot take vitamin C in, the vitamin cannot restore the enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[liu-2020] Decreased vitamin C uptake mediated by SLC2A3 promotes leukaemia progression and impedes TET2 restoration (2020). https://pubmed.ncbi.nlm.nih.gov/32203209/ DOI: 10.1038/s41416-020-0788-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Leukaemic blasts","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4f0a7513-fbbb-5524-8b40-c4f4a845e7ed","evidence_kind":"source_excerpt","locator":"Lines 163-171","start_line":163,"end_line":171,"excerpt":"## slc2a3-gates-vitamin-c-tet2-restoration\nIn patient-derived primary acute-myeloid-leukaemia cells, vitamin C restored TET2 activity only when SLC2A3 was expressed, and SLC2A3 knockdown in the KG-1 cell line decreased the response to vitamin C.\nModel/species: AML cell lines, an SLC2A3-knockdown line and patient-derived primary AML cells; TCGA and TARGET expression analysis\nOrganism: Homo sapiens\nTissue/system: Leukaemic blasts\nExposure: Vitamin C, with and without SLC2A3 knockdown\nDuration: Culture experiments\nLimits: Below-median SLC2A3 expression was associated with poorer overall survival, which is an association within a database cohort and not an experimental outcome.\nPrimary reference: [liu-2020] Decreased vitamin C uptake mediated by SLC2A3 promotes leukaemia progression and impedes TET2 restoration (2020). https://pubmed.ncbi.nlm.nih.gov/32203209/ DOI: 10.1038/s41416-020-0788-8","model_system":"AML cell lines, an SLC2A3-knockdown line and patient-derived primary AML cells; TCGA and TARGET expression analysis","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}