Hierarchical relationships between LSCs in CD34⁺and CD34⁻AML at diagnosis. Xenograft models suggest that CD34⁺ AML is arranged in a semihierarchical structure resembling normal hematopoiesis (left). In many patients, there is an increased LSC frequency in the CD34⁺CD38⁻ population, which in turn gives rise to a CD34⁺CD38⁺ population with a reduced LSC frequency, but reversible plasticity is likely to be present in many cases. In infrequent cases, CD34⁻ cells also contain rare LSCs. In CD34⁻ AML, CD34⁺ and CD34⁻ populations have similar LSC frequencies and gene expression profiles that most resemble precursor GM cells (right). The CD34⁻ LSCs may express progenitor markers such as CD117 and myeloid antigens such as CD15 and CD244, and both in turn give rise to a non-LSC population with a mature myeloid immunophenotype.