AML1/ETO Confers a Mutator Phenotype in AML

The translocation t(8;21), resulting in the AML1/ETO (AE) fusion gene is the most common cytogenetic abnormality in acute myeloid leukaemia(AML). In animal models, AE expression is insufficient for leukaemogenesis with further mutations required for leukaemic transformation. Ectopic expression of AE in TK6 and HL60 cell lines results in ˜2-fold down-regulation of the gene OGG1, a DNA glycosylase which removes damaged guanine bases from DNA. Knock-down of AE in Kasumi-1 increased OGG1 substantially, providing strong evidence that AE directly regulates OGG1. TK6 AE were cloned to give varying AE expression and ana…