Hematopoietic transcription factor gene mutations and inherited platelet defects

Abstract

Hematopoietic transcription factors (TF) are proteins that bind to specific DNA sequences and regulate expression of genes. Hematopoietic TF act in a combinatorial manner to bind sequence-specific DNA within promoter regions to regulate specific gene expression, either as activators or repressors. Hematopoietic TF gene mutations induce rippling downstream effects by simultaneously altering the expression of multiple genes. Mutations involving these hematopoietic TF affect diverse aspects of megakaryocyte biological function, and platelet production and function, culminating in thrombocytopenia and platelet dysfunction. Some hematopoietic TF mutations are associated with predisposition to hematologic malignancies. The molecular and genetic mechanisms in inherited platelet defects (IPD) are unknown. A growing number of evidences suggest that hematopoietic TF gene mutations are important underlying causes for defects in platelet production, morphology and function. The review summarizes the current scientific progress of hematopoietic TF gene mutations in IPD. Key words: Transcription factors; Hematopoietic system; Mutation; Blood platelet disorders; Thrombocytopenia; Inherited platelet defects