
<ArticleTitle>Detection and clinical significance of human acute myeloid leukaemia progenitors capable of long-term proliferation in vitro.</ArticleTitle>
<AbstractText>Acute myeloid leukaemia (AML) blasts within individual patients are heterogeneous in their surface antigen expression and proliferative ability suggesting that, subsequent to transformation, differentiation occurs creating a hierarchy of progenitors in AML. Cells that can produce AML colonies (colony forming units, CFU) in growth factor containing suspension cultures (SC) over 4-8 weeks have a phenotype similar to AML progenitors that engraft non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, but different from bulk AML blasts, suggesting that these AML SC-initiating cells (SC-IC) may be early progenitors. In this study, we evaluated culture conditions that provide for optimal growth of AML progenitors capable of long-term proliferation. The frequency of CFU, both initially and after 2-4 weeks of SC, varied over four logs between individual patients and was not related to French-American-British subtype. Using limiting dilution, the proliferative potential of individual SC-IC varied from 1 to 480 CFU. The frequency of CFU from SC after  4 weeks was prognostic for patient survival, and correlated with NOD/SCID engrafting ability. These results suggest the use of long-term culture as an assay for AML cells with leukaemia sustaining potential.</AbstractText>
