ETS variant transcription factor 6-Platelet-derived growth factor receptor beta fusion protein (ETV6-PDGFRB) (ETV6-PDGFRB)

The ETV6-PDGFRB fusion protein is a chimeric tyrosine kinase resulting from the t(5;12)(q33;p13) chromosomal translocation (Golub et al., 1994, Cell). This genetic rearrangement fuses the N-terminal sterile alpha motif (SAM) domain of the ETV6 (TEL) transcription factor to the transmembrane and cytoplasmic kinase domains of the Platelet-derived growth factor receptor beta (PDGFRB). The SAM domain facilitates constitutive oligomerization of the protein, leading to ligand-independent activation of the PDGFRB kinase domain and subsequent stimulation of downstream signaling pathways like PI3K/AKT, MAPK, and STAT5 (Carroll et al., 1996, PNAS). This aberrant signaling drives the pathogenesis of certain myeloproliferative neoplasms, particularly chronic myelomonocytic leukemia (CMML) with eosinophilia. ETV6-PDGFRB is a significant therapeutic target because its kinase activity is potently inhibited by tyrosine kinase inhibitors such as imatinib, which often leads to complete hematologic and cytogenetic remissions in affected patients (Apperley et al., 2002, NEJM; NIH/NCI). Monitoring of the fusion transcript via quantitative RT-PCR is essential for assessing treatment response and minimal residual disease.

Other names

TEL-PDGFRBTEL-PDGFRt(5;12)(q33;p13) fusion proteinETV6-PDGFRB chimeric protein

Tyrosine kinase inhibition via competitive binding to the ATP-binding site of the PDGFRB kinase domain, preventing autophosphorylation and downstream signaling (Apperley et al., 2002, NEJM).