ETV6 fusion genes in hematological malignancies: a review

Leukemia Research
Etienne De BraekeleerMarc De Braekeleer

Abstract

Translocations involving band 12p13 are one of the most commonly observed chromosomal abnormalities in human leukemia and myelodysplastic syndrome. Their frequently result in rearrangements of the ETV6 gene. At present, 48 chromosomal bands have been identified to be involved in ETV6 translocations, insertions or inversions and 30 ETV6 partner genes have been molecularly characterized. The ETV6 protein contains two major domains, the HLH (helix-loop-helix) domain, encoded by exons 3 and 4, and the ETS domain, encoded by exons 6 through 8, with in between the internal domain encoded by exon 5. ETV6 is a strong transcriptional repressor, acting through its HLH and internal domains. Five potential mechanisms of ETV6-mediated leukemogenesis have been identified: constitutive activation of the kinase activity of the partner protein, modification of the original functions of a transcription factor, loss of function of the fusion gene, affecting ETV6 and the partner gene, activation of a proto-oncogene in the vicinity of a chromosomal translocation and dominant negative effect of the fusion protein over transcriptional repression mediated by wild-type ETV6. It is likely that ETV6 is frequently involved in leukemogenesis because of the...Continue Reading

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