Topoisomerase-II inhibition leads to DNA breakage at fragile spots, with frequent improper repairs of these breaks, chromosomal translocations such as t(11q23;var) on the MLL gene and likely on other leukemia-associated genes (e.g. RUNX1, etc.)allowing these hematopoietic stem cells (HSCs) to escape apoptosis and lead to clonal expansion and the development of therapy-related leukemias. This evidence concerns the gene RUNX1 and leukemia.