Etoposide induces chimeric Mll gene fusions

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Abstract
SPECIFIC AIMOur aim was to determine if we could detect the formation of chimeric Mll gene fusions in intact mammalian cells following etoposide treatment, to characterize any such fusion partners, and to determine whether such fusions were detectable after chemotherapy whose mechanism does not include topoisomerase II inhibition.PRINCIPAL FINDINGS1. Etoposide causes formation of Mll fusions whereas vincristine does notIn humans, topoisomerase II inhibitor-induced therapy-related acute leukemia is characterized by chimeric MLL gene fusions, with the vast majority of fusion points occurring in an 8.3-kb breakpoint cluster region (BCR) that encompasses exons 5 through 11. However, MLL partners with over 40 different genes to create leukemogenic gene fusions. The strategy to detect possible etoposide-induced murine Mll chimeric fusions, without bias as to the partner gene, is presented in the overall schematic depicted in Fig. 1⤻ . Amplification of the circularized Mll BCR germline fragment yields a single b...
Funding Information
  • American Lebanese Syrian Associated Charities