ETV6 in hematopoiesis and leukemia predisposition

Abstract

The ETV6 (also known as TEL) gene encodes a transcriptional repressor that plays a critical role in hematopoiesis and in embryonic development. While somatic ETV6 translocations and missense mutations are frequently observed in human cancers, the role of ETV6 in malignant transformation was unclear. Recently, autosomal dominant germline ETV6 mutations were discovered in families with inherited thrombocytopenia and a propensity to develop hematological malignancy, unequivocally demonstrating a role for ETV6 in leukemogenesis. Studies of germline ETV6 mutations also uncovered an important function of ETV6 in megakaryocyte development. Here we discuss our current understanding of the role of ETV6 in malignancy and in hematopoiesis.

Keywords: ALL; ETV6; MDS; Platelets; TEL; Thrombocytopenia.

Figure 1. ETV6 structure and location of familial ETV6 mutations

The ETV6 structural domains and locations of familial mutations are shown. The N-terminal pointed domain (PNT) mediates oligomerization with itself as well as with other factors. The C-terminal DNA-binding domain (ETS) is conserved among ETS-family transcription factors. The majority of the mutations identified in family studies cluster within the ETS domain. The P214L mutation, which resides in the linker region, has been recurrently identified in different families.