{"id":"d5ffe335-9ce8-5e0d-8db0-2998c88f38b0","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-depletion-accelerates-leukaemogenesis","predicate":"depletion_increases","statement":"Systemic ascorbate depletion cooperated with Flt3 internal tandem duplication to accelerate leukaemogenesis in mice, and restoring dietary ascorbate reversed that acceleration.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"aadf7484-944d-523d-a288-85c737a2f793","mechanism_event_label":"Systemic ascorbate depletion cooperated with Flt3 internal tandem duplication to accelerate leukaemogenesis in mice, and restoring dietary ascorbate reversed that acceleration.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"013b4433-ba68-5dd7-93ad-5415c3918b7b","slug":"mouse-flt3itd-leukaemogenesis","display_name":"Leukaemogenesis in Flt3-internal-tandem-duplication mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"aadf7484-944d-523d-a288-85c737a2f793","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:ascorbate-depletion-accelerates-leukaemogenesis-event","event_type":"observed_relationship","label":"Systemic ascorbate depletion cooperated with Flt3 internal tandem duplication to accelerate leukaemogenesis in mice, and restoring dietary ascorbate reversed that acceleration.","description":"In mice already carrying a leukaemia mutation, vitamin C shortage made the disease come faster, and feeding it back undid that.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"013b4433-ba68-5dd7-93ad-5415c3918b7b","slug":"mouse-flt3itd-leukaemogenesis","display_name":"Leukaemogenesis in Flt3-internal-tandem-duplication mice","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"To leukaemia onset","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ascorbate-depleted mice carrying Flt3 internal tandem duplication","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Dietary ascorbate depletion, with dietary ascorbate restoration as the reversal arm","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Depletion acted together with a leukaemic driver mutation; this is not evidence that ascorbate shortage alone causes leukaemia. The authors note possible non-cell-autonomous mechanisms.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In mice already carrying a leukaemia mutation, vitamin C shortage made the disease come faster, and feeding it back undid that.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[agathocleous-2017] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis (2017). https://pubmed.ncbi.nlm.nih.gov/28825709/ DOI: 10.1038/nature23876","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Haematopoietic system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"f7083e27-37e6-5e3f-9565-daa6fccb95c9","evidence_kind":"source_excerpt","locator":"Lines 133-141","start_line":133,"end_line":141,"excerpt":"## ascorbate-depletion-accelerates-leukaemogenesis\nSystemic ascorbate depletion cooperated with Flt3 internal tandem duplication to accelerate leukaemogenesis in mice, and restoring dietary ascorbate reversed that acceleration.\nModel/species: Ascorbate-depleted mice carrying Flt3 internal tandem duplication\nOrganism: Mus musculus\nTissue/system: Haematopoietic system\nExposure: Dietary ascorbate depletion, with dietary ascorbate restoration as the reversal arm\nDuration: To leukaemia onset\nLimits: Depletion acted together with a leukaemic driver mutation; this is not evidence that ascorbate shortage alone causes leukaemia. The authors note possible non-cell-autonomous mechanisms.\nPrimary reference: [agathocleous-2017] Ascorbate regulates haematopoietic stem cell function and leukaemogenesis (2017). https://pubmed.ncbi.nlm.nih.gov/28825709/ DOI: 10.1038/nature23876","model_system":"Ascorbate-depleted mice carrying Flt3 internal tandem duplication","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}