{"id":"caef534b-9059-506b-a9af-d5b25cc1da8c","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-aml-silencing","predicate":"creates_dependency_on","statement":"ISYNA1 transcriptional silencing characterized SLC5A3-dependent AML lines and produced an inositol auxotrophy.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2758e0cf-1ac6-52cc-829f-792266709bcd","mechanism_event_label":"When a cell loses its synthesis route, the import route can become essential.","subject":{"id":"f0e0d47f-b360-5916-82a3-e6f2dfd5f184","slug":"isyna1-silencing","display_name":"ISYNA1 transcriptional silencing","entity_type_key":"cellular_process"},"object":{"id":"5453efb2-0a63-560e-9a73-69113a43bd5b","slug":"slc5a3","display_name":"SLC5A3 (human SMIT1)","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"2758e0cf-1ac6-52cc-829f-792266709bcd","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-aml-silencing-event","event_type":"biochemical_relationship","label":"When a cell loses its synthesis route, the import route can become essential.","description":"ISYNA1 transcriptional silencing characterized SLC5A3-dependent AML lines and produced an inositol auxotrophy.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"50afe95c-f542-5511-ba8b-c2ff2b037977","slug":"myo-inositol","display_name":"Myo-inositol","entity_type_key":"small_molecule"},"role":"required_metabolite","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f0e0d47f-b360-5916-82a3-e6f2dfd5f184","slug":"isyna1-silencing","display_name":"ISYNA1 transcriptional silencing","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5453efb2-0a63-560e-9a73-69113a43bd5b","slug":"slc5a3","display_name":"SLC5A3 (human SMIT1)","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/inositol-research/34531253.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27\", \"start_char\": 0, \"end_char\": 1431, \"text_sha256\": \"e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Genetic screening, gain/loss of function and patient sample profiling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SLC5A3/ISYNA1 perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Inositol research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"inositol","display_name":"Inositol (stereoisomer family)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human AML cells and in vivo leukemia models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"When a cell loses its synthesis route, the import route can become essential.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. (2022). https://pubmed.ncbi.nlm.nih.gov/34531253/ DOI: 10.1158/2159-8290.cd-20-1849","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Acute myeloid leukemia","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"87b725ce-3457-5eae-a3de-9e3a90200065","evidence_kind":"source_excerpt","locator":"Lines 405-416","start_line":405,"end_line":416,"excerpt":"### ino-aml-silencing\nISYNA1 transcriptional silencing characterized SLC5A3-dependent AML lines and produced an inositol auxotrophy.\nCondition category: machinery_impairment\nnutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: When a cell loses its synthesis route, the import route can become essential.\norganism: Human AML cells and in vivo leukemia models\ntissue_or_cell_type: Acute myeloid leukemia\nexperimental_model: Genetic screening, gain/loss of function and patient sample profiling\nlimitations: Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia.\nexposure: SLC5A3/ISYNA1 perturbation\nevidence_span: {\"source_cache\": \"artifacts/inositol-research/34531253.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27\", \"start_char\": 0, \"end_char\": 1431, \"text_sha256\": \"e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27\"}\n[ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. 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