Leukemias are composed of a hierarchy of cells, only a fraction of which have stem cell-like properties and are capable of self-renewal. Mixed lineage leukemia (MLL) fusion proteins produced by translocations involving the MLL gene on chromosome 11q23 confer stem cell-like properties on committed hematopoietic progenitors. This provides an opportunity to assess changes in immunophenotype, gene expression, and epigenetic programs during the transition from a hematopoietic cell with minimal inherent self-renewal capability to cells capable of leukemic self-renewal.