title: Detection and clinical significance of human acute myeloid leukaemia progenitors capable of long-term proliferation in vitro.
abstract: 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.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver Hospital and Health Sciences Center, British Columbia, Canada. hsutherl@bccancer.bc.ca
authors.forename: H
authors.initials: H
authors.lastname: Sutherland
authors.forename: A
authors.initials: A
authors.lastname: Blair
authors.forename: S
authors.initials: S
authors.lastname: Vercauteren
authors.forename: R
authors.initials: R
authors.lastname: Zapf
mesh_terms: D000208:Acute Disease; D000818:Animals; D002455:Cell Division; D003114:Colony-Forming Units Assay; D018572:Disease-Free Survival; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000473:pathology*; D007958:Leukocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023461:Myeloid Progenitor Cells / Q000473:pathology*; D011379:Prognosis; D012044:Regression Analysis; D013997:Time Factors