ETV6-related thrombocytopenia: dominant negative effect of mutations as common pathogenic mechanism

Abstract

Inherited thrombocytopenias are a group of rare diseases characterized by low platelet count and variable bleeding tendency. In some forms, patients might develop additional phenotypes during life, such as myeloid neoplasms as in ETV6-related thrombocytopenia (ETV6-RT). ETV6-RT is caused by germline heterozygous mutations of ETV6, a gene encoding a master hematopoietic transcriptional repressor structured in three functional domains: the N-terminal pointed (PNT), the central regulatory domain (CRD) and C-terminal DNA-binding (ETS).