Abstract

Secondary leukemia is a severe side effect that affects 2–8% of cancer patients treated with etoposide, a topoisomerase II inhibitor. Genomic aberrations associated with acute myeloid leukemia, such as chromosomal translocation (8;21), are often found in those patients. This suggests that myeloid cells, including bone marrow and peripheral blood cells, are affected more than other cell types by the action of etoposide. However, the exact mechanism behind the generation of that particular type of cancer largely unknown. Moreover, intravenous administration of etoposide implies that peripheral blood cells are the first cells that come in contact with the drug. Therefore, we hypothesize that treatment with etoposide generates specific genomic aberrations in RUNX1 intron five in circulating blood cells. To test this hypothesis, we assessed genomic aberrations using inverse genomic polymerase chain reaction on DNA from samples of periph-eral blood treated with clinically relevant concentrations ofetoposide. Surprinsingly, our results show that genomic aberrations in RUNX1 gene due to treatment with etoposide are not completely random, suggesting that this may be the first step towards cell transformation.