{"id":"ba5ce67d-0eb8-54d0-946e-36de88f98aaf","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-defect-precedes-jak2-v617f","predicate":"is_acquired_before","statement":"TET2 defects were present in haematopoietic stem cells and preceded the JAK2 V617F mutation in the five analysed samples from patients with myeloproliferative disorders.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"292cf9e8-6b8e-575b-8cb9-cb6843208a3c","mechanism_event_label":"TET2 defects were present in haematopoietic stem cells and preceded the JAK2 V617F mutation in the five analysed samples from patients with myeloproliferative disorders.","subject":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"object":{"id":"726c87fd-dc24-5254-b518-8a92a1e5efb7","slug":"human-mpn-jak2-clone-order","display_name":"Order of TET2 and JAK2 V617F acquisition in human myeloproliferative clones","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"292cf9e8-6b8e-575b-8cb9-cb6843208a3c","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:tet2-defect-precedes-jak2-v617f-event","event_type":"observed_relationship","label":"TET2 defects were present in haematopoietic stem cells and preceded the JAK2 V617F mutation in the five analysed samples from patients with myeloproliferative disorders.","description":"Where both were present, the TET2 damage came first.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5433ea92-f679-5b25-a872-cb8a636ae4e1","slug":"tet2-human","display_name":"Human TET2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"726c87fd-dc24-5254-b518-8a92a1e5efb7","slug":"human-mpn-jak2-clone-order","display_name":"Order of TET2 and JAK2 V617F acquisition in human myeloproliferative clones","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Cross-sectional","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Five myeloproliferative-disorder patient samples with clonal analysis of progenitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"No intervention; clonal ordering within patient samples","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Five samples. Order of acquisition in a clone does not by itself establish which lesion drives the disease.","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":"Where both were present, the TET2 damage came first.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[delhommeau-2009] Mutation in TET2 in myeloid cancers (2009). https://pubmed.ncbi.nlm.nih.gov/19474426/ DOI: 10.1056/nejmoa0810069","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Haematopoietic stem and progenitor cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f45cb7f7-793c-571a-9b71-d25400e73dfe","evidence_kind":"source_excerpt","locator":"Lines 23-31","start_line":23,"end_line":31,"excerpt":"## tet2-defect-precedes-jak2-v617f\nTET2 defects were present in haematopoietic stem cells and preceded the JAK2 V617F mutation in the five analysed samples from patients with myeloproliferative disorders.\nModel/species: Five myeloproliferative-disorder patient samples with clonal analysis of progenitors\nOrganism: Homo sapiens\nTissue/system: Haematopoietic stem and progenitor cells\nExposure: No intervention; clonal ordering within patient samples\nDuration: Cross-sectional\nLimits: Five samples. Order of acquisition in a clone does not by itself establish which lesion drives the disease.\nPrimary reference: [delhommeau-2009] Mutation in TET2 in myeloid cancers (2009). https://pubmed.ncbi.nlm.nih.gov/19474426/ DOI: 10.1056/nejmoa0810069","model_system":"Five myeloproliferative-disorder patient samples with clonal analysis of progenitors","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}