ETV6

ETV6, also known as TEL, is a gene encoding a transcription factor of the ETS family. It resides on chromosome 12p13 and encodes a protein with an N-terminal pointed (PNT) domain and a C-terminal ETS DNA-binding domain. The protein generally acts as a transcriptional repressor and participates in hematopoietic and vascular development by regulating target genes.

The PNT domain mediates dimerization and protein interactions, enabling transcriptional repression through recruitment of corepressors and chromatin modifiers. ETV6 influences differentiation of hematopoietic lineages, especially megakaryocytic and erythroid cells, and can suppress cell proliferation under certain conditions. Its activity is context-dependent, and disruption can contribute to tumorigenesis.

ETV6 is a common target of chromosomal translocations in cancers. The t(12;21) translocation yields the ETV6-RUNX1 fusion (TEL-AML1), frequent in pediatric B-ALL and associated with favorable prognosis in some risk groups. Other fusions include ETV6-NTRK3, seen in congenital fibrosarcoma and secretory breast carcinoma, and ETV6-ABL1, identified in leukemias and some myeloproliferative neoplasms. These rearrangements often drive oncogenesis by creating constitutive signaling or dysregulated transcriptional programs.

Genetics and research: ETV6 rearrangements serve as diagnostic and prognostic markers and can inform therapy. The gene is widely expressed, with notable activity in hematopoietic tissues; multiple transcripts exist. Therapeutic implications include targeting kinase activity driven by certain fusions, such as NTRK inhibitors for ETV6-NTRK3 or ABL inhibitors in ETV6-ABL1 cases. Ongoing studies continue to elucidate ETV6’s broader role in normal physiology and cancer.