Inherited Platelet Defects and Mutations in Hematopoietic Transcription Factor RUNX1

Abstract

Increasing evidence implicates mutations in hematopoietic transcription factors (TFs) as an important cause for inherited defects in platelet production, morphology, and function. TFs are proteins that bind to specific DNA sequences and regulate gene expression, with each TF regulating numerous genes. They act in a combinatorial manner to bind sequence-specific DNA within promoter regions to regulate lineage-specific gene expression, either as activators or repressors. The hematopoietic TFs associated with impaired platelet function and number include the runt related transcription factor 1 (RUNX1), Fli-1 proto-oncogene, ETS transcription factor (FLI1), GATA-binding protein 1 (GATA1), growth factor independent 1B transcriptional repressor (GFI1B), ETS variant 6 (ETV6), ecotropic viral integration site 1 (EVI1), and homeobox A11 (HOXA11). Mutations involving these TFs affect diverse aspects of megakaryocyte and platelet biology, leading to thrombocytopenia, platelet dysfunction, and often both. Some are associated with predisposition to hematologic malignancies. This review focuses on the inherited platelet abnormalities associated with mutations in RUNX1.