title: Transcription factor defects causing platelet disorders.
abstract: Recent years have seen increasing recognition of a subgroup of inherited platelet function disorders which are due to defects in transcription factors that are required to regulate megakaryopoiesis and platelet production. Thus, germline mutations in the genes encoding the haematopoietic transcription factors RUNX1, GATA-1, FLI1, GFI1b and ETV6 have been associated with both quantitative and qualitative platelet abnormalities, and variable bleeding symptoms in the affected patients. Some of the transcription factor defects are also associated with an increased predisposition to haematologic malignancies (RUNX1, ETV6), abnormal erythropoiesis (GATA-1, GFI1b, ETV6) and immune dysfunction (FLI1). The persistence of MYH10 expression in platelets is a surrogate marker for FLI1 and RUNX1 defects. Characterisation of the transcription factor defects that give rise to platelet function disorders, and of the genes that are differentially regulated as a result, are yielding insights into the roles of these genes in platelet formation and function.
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK. Electronic address: m.daly@sheffield.ac.uk.
authors.forename: Martina E
authors.initials: ME
authors.lastname: Daly
mesh_terms: D001791:Blood Platelet Disorders / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D004198:Disease Susceptibility; D005786:Gene Expression Regulation; D018095:Germ-Line Mutation; D006487:Hemostasis; D006801:Humans; D013329:Structure-Activity Relationship; D034061:Thrombopoiesis / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014157:Transcription Factors
keywords: ETV6; FLI1; GATA-1; GFI1b; Platelet disorders; RUNX1; Transcription factor defects