In addition to the discovery of new, intermittently mutated genes (e.g., WAC, SMC3, DIS3, DDX41, and DAXX) in AML, two major patterns of clonal evolution during AML relapse were also found: (1) the founder clone in the primary tumor acquired mutations and evolved into a clone of relapse, or (2) a minor subclone of the founder clone survived the initial therapy, acquired additional mutations, and proliferated at relapse. This evidence concerns the gene DDX41 and acute myeloid leukemia.