The mouse niche may not support human HSCs in xenograft models. Mouse HSCs interact with the niche, which promotes quiescence. Several observations suggest that the mouse niche does not support human HSCs to maintain quiescence and stemness. As a result, human HSCs are proliferative in xenograft models, which leads to HSC differentiation. Human LSCs from aggressive types of leukemia do not appear to require the support from the mouse niche to maintain leukemic growth.