Secondary mutations in t(4;11) leukemia patients

MLL rearrangements are a genetic hallmark of acute leukemia patients, which exhibit a particular poor outcome. To date, more than 70 MLL rearrangements have been described at the molecular level. 1 For the most frequently diagnosed MLL rearrangements, for example, AF4-MLL , MLL-AF9 , MLL-AF10 or MLL-ENL , it has been shown that these fusion proteins are sufficient for acute leukemia onset in murine model systems. 2 However, these models had a latency time of 4–12 months for the disease phenotype to become overt. This argues in favor of pre-leukemic clones that carry the fusion genes, but need, in addition, complementing mutations to develop a malignant disease.