Hierarchy of leukemia stem cells in AML. Like the normal hematopoietic system, AML is organized as a hierarchy of distinct cell classes that is sustained by a subset of leukemia stem cells (or SCID-leukemia initiating cells [SL-ICs], as assayed in immunodeficient mice). Genetic tracking experiments have shown that SL-ICs are heterogeneous in their ability to repopulate secondary and tertiary recipients, pointing to the existence of distinct classes with differing self-renewal capacity, similar to what is seen in the normal hematopoietic stem cell compartment. Short-term (ST) SL-ICs are able to initiate leukemia in primary but not secondary recipients, whereas long-term (LT) SL-ICs can sustain leukemic growth for multiple passages. Quiescent LT SL-ICs may not initiate a substantial graft in primary recipients and may therefore only be detected on serial transplantation.