Figure 2: Schematic illustration of the normal and leukaemic human haematopoietic hierarchies. Human haematopoietic cells are organized in a hierarchy that is sustained by a small population of self-renewing HSCs. HSCs give rise to progressively more lineage-restricted, differentiated progenitors with reduced self-renewal capacity (LTC-ICs, long-term culture-initiating cells; CFU, colony-forming units), which in turn produce functionally mature blood cells. Disruption of pathways regulating self-renewal and differentiation through the acquisition of transforming mutations generates LSCs capable of sustaining growth of the leukaemic clone in vivo. LSCs possess an altered differentiation program, as demonstrated by aberrant expression of some cell-surface markers (indicated in purple) and give rise to an aberrant developmental hierarchy that retains aspects of its normal counterpart. In vivo, reconstitution assays using immune-deficient mouse recipients enable detection of HSCs and LSCs as SCID-repopulating cells (SRCs) and SCID leukaemia-initiating cells (SL-ICs), respectively [39].