Chronic myelogenous leukaemia CD34+ cells exit G0/G1 phases of cell cycle more rapidly than normal marrow CD34+ cells

Authors

  • Christie M. Traycoff,

    1. Bone Marrow Transplant Program, Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
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  • Bartley Halstead,

    1. Bone Marrow Transplant Program, Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
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  • Susan Rice,

    1. Bone Marrow Transplant Program, Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
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  • Jon Mcmahel,

    1. Bone Marrow Transplant Program, Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
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  • Edward F. Srour,

    1. Bone Marrow Transplant Program, Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
    2. Division of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
    3. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
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  • Kenneth Cornetta

    1. Bone Marrow Transplant Program, Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
    2. Division of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
    3. Division of Medical and Molecular Genetics, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.,
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Dr Christie M. Traycoff Indiana University School of Medicine, 1044 W. Walnut Street, R4-202, Indianapolis, IN 46202-5121, U.S.A.

Abstract

To investigate the mechanisms behind the leukaemic expansion of chronic myelogenous leukaemia (CML), we examined the cell cycle status and activation kinetics of purified subpopulations of CD34+ cells from normal and CML bone marrow (BM). Propidium iodide staining was used to assess cell cycle status of fresh cells or those stimulated with cytokines. Although the cell cycle status of fresh low-density cells from CML and normal BM was similar, a larger percentage of CML CD34+ cells were cycling than those from normal BM. The HLA-DR compartment of CML CD34+ cells, a fraction enriched for normal, non-leukaemic progenitors, contained a higher percentage of quiescent cells than the CD34+ HLA-DR+ fraction. When the activation of CD34+ cells was examined in response to SCF or IL-3 alone, or SCF+IL-3+IL-6, CML CD34+ cells exited G0/G1 more rapidly than normal CD34+ cells. Interestingly, although normal BM CD34+ cells failed to cycle in response to IL-6 alone, or in the absence of exogenous cytokines, 30% of CML cells cycled under these conditions. No differences in the degree of apoptosis were documented among CML and normal CD34+ cells in these cultures. These data suggest that enhanced cell cycle activation of CML CD34+ cells, by either autocrine stimuli or via enhanced sensitivity to exogenous stimuli, may be partially responsible for the pronounced cellular expansion characteristic of CML.

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