CHRONIC MYELOGENOUS LEUKEMIA CD34(-CYCLE MORE RAPIDLY THAN NORMAL MARROW CD34(+) CELLS() CELLS EXIT G(0)G(1) PHASES OF CELL)

To investigate the mechanisms behind the leukaemic expansion of chroni c myelogenous leukaemia (CML), we examined the cell cycle status and a ctivation kinetics of purified subpopulations of CD34(+) cells from no rmal and CML bone marrow (BM). Propidium iodide staining was used to a ssess cell cycle status of fresh cells or those stimulated with cytoki nes. Although the cell cycle status of fresh low-density cells from CM L 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 progenit ors. contained a higher percentage of quiescent cells than the CD34(+) HLA-DR+ fraction. When the activation of CD34(+) cells was examined i n response to SCF or IL-3 alone, or SCF+IL-3+IL-6, CML CD34(+) cells e xited G(0)/G(1) 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 cycl ed under these conditions. No differences in the degree of apoptosis w ere documented among CML and normal CD34(+) cells in these cultures. T hese data suggest that enhanced cell cycle activation of CML CD34(+) c ells, by either autocrine stimuli or via enhanced sensitivity to exoge nous stimuli, may be partially responsible for the pronounced cellular expansion characteristic of CML.