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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-10-3062. This Article Full Text (PDF) All Versions of this Article: 2002-10-3062v1 101/8/3142    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Guan, Y. Articles by Hogge, D. E Search for Related Content PubMed PubMed Citation Articles by Guan, Y. Articles by Hogge, D. E Social Bookmarking                   What's this? Submitted October 8, 2002 Accepted November 22, 2002 Detection, Isolation and Stimulation of Quiescent Primitive Leukemic Progenitor Cells from Patients with Acute Myeloid Leukemia (AML) Yinghui Guan, Brigitte Gerhard, and Donna E Hogge* Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada * Corresponding author; email: dhogge{at}bccancer.bc.ca. Although many acute myeloid leukemia (AML) colony forming cells (CFC) and long-term culture-initiating cells (LTC-IC) directly isolated from patients are actively cycling, quiescent progenitors are present in most samples. In the current study 3H-Tdr suicide assays demonstrated that the majority of NOD/SCID mouse leukemia-initiating cells (NOD/SL-IC) are quiescent in 6 of 7 AML samples. AML cells in G, G1 and S/G2+M were isolated from 4 of these samples using Hoechst 33342/pyroninY staining and cell sorting. The progenitor content of each subpopulation was consistent with the 3H-Tdr suicide results with NOD/SL-IC found almost exclusively among G cells while the cycling status of AML CFC and LTC-IC was more heterogeneous. Interestingly, after 72h in serum free culture with or without Steel factor (SF), Flt-3 ligand (FL) and interleukin-3 (IL-3) most G0 AML cells entered active cell cycle (% AML cells remaining in G at 72h, 1.2% - 37%, and 0% - 7.6% in cultures without and with growth factors (GF), respectively) while G cells from normal lineage depleted bone marrow remained quiescent in the absence of GF. All 4 AML samples showed evidence of autocrine production of two or more of SF, FL, IL-3, and GM-CSF. In addition, 3 of 4 samples contained an internal tandem duplication of the FLT3 gene. In summary, quiescent leukemic cells, including NOD/SL-IC, are present in most AML patients. 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