Transcription factor ETV6 (ETV6) (ETV6)

Transcription factor ETV6 (ETS variant transcription factor 6), also known as TEL, is a sequence-specific transcriptional repressor essential for embryonic development and adult hematopoiesis [1, 5]. It belongs to the ETS family and is characterized by an N-terminal pointed (PNT) domain for protein-protein interaction and a C-terminal ETS domain for DNA binding [4, 6]. ETV6 is a frequent target of chromosomal translocations in human malignancies, where its PNT domain facilitates the constitutive activation of various partner tyrosine kinases, such as NTRK3 and PDGFRB, leading to leukemias and solid tumors [2, 7]. Germline mutations in ETV6 are associated with Thrombocytopenia 5 and a significant predisposition to hematologic cancers, particularly B-cell acute lymphoblastic leukemia [3, 14, 19]. While direct pharmacological targeting of ETV6 is difficult, therapeutic approaches primarily utilize tyrosine kinase inhibitors like larotrectinib or imatinib to inhibit its oncogenic fusion products [2, 7]. Recent studies also suggest that ETV6 may be a viable target in Ewing sarcoma by modulating the activity of the EWS-FLI1 fusion protein [8].

Other names

TELTEL1ETS variant 6ETS-related protein Tel1Translocation-Ets-leukemiaETS variant transcription factor 6ETS translocation variant 6TEL oncogene

Inhibition of the kinase activity of ETV6 fusion partners (e.g., NTRK, PDGFRB, JAK2) which are constitutively activated by the ETV6 oligomerization domain; experimental disruption of ETV6-mediated transcriptional regulation or protein-protein interactions.