Molecular pathogenesis of disease progression in MLL-rearranged AML

Leukemic relapse is frequently accompanied by progressively aggressive clinical course. To understand the molecular mechanism of leukemic relapse, MLL/AF9 -transformed mouse leukemia cells were serially transplanted in C57BL/6 mice ( N = 96) by mimicking repeated recurrences, where mutations were monitored by exome sequencing ( N = 42). The onset of leukemia was progressively promoted with advanced transplants, during which increasing numbers of somatic mutations were acquired ( P