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Early T cell precursor acute lymphoblastic leu-kemia (ETP-ALL) is a recently described subtype of acute lymphoblastic leukemia that occurs in both adults and children and has a relatively poor survival rate with current therapies (Coustan-Smith et al., 2009). The leukemic blasts in ETP-ALL have a unique phenotype characterized by cytoplasmic expression of CD3, a lack of expres-sion of mature T cell markers such as CD4 and CD8, and aberrant expression of myeloid and stem cell markers. There has been no animal model for ETP-ALL, so the biology of the dis-ease and identification of new therapeutics re-mains relatively unexplored. The prevailing hypothesis is that ETP-ALL is caused by transformation of a primitive hema-topoietic cell that retains the capacity to differ-entiate into both T cells and myeloid cells. The thymus is seeded by primitive thymic immigrants derived from the BM that then proceed through a series of maturational steps, ultimately gen-erating CD4 and CD8 single-positive T cells (Rothenberg et al., 2010). The initial stages of thymocyte development are characterized by differentiation of cells that lack expression of CD4 or CD8. As these double negative (DN) cells differentiate, at least four distinct differen-tiation stages can be distinguished by differential expression of CD44 and CD25 (DN1, DN2, DN3, and DN4). The potential for myeloid, dendritic, and natural killer cell differentiation is retained at the DN1 stage and at the early DN2 stage (Bell and Bhandoola, 2008). The ability to adopt non–T cell fates is lost by the DN3 stage and most likely by the latter half o