Stage-specific alterations in serum levels of G-CSF in chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) is a myeloproliferative disease of stem cell origin, characterised by the presence of the Philadelphia (Ph) chromosome and a BCR–ABL fusion gene that is believed to be causal to the disease. CML cells display changes in many intracellular signalling pathways normally activated by growth factor receptors, suggesting a variety of mechanisms by which these cells might acquire reduced dependence on normal growth factor stimulation or decreased responsiveness to inhibitory factors. This is now known to involve the autocrine production of growth factors, specifically IL-3 and G-CSF, by the CD34<sup>+</sup> leukaemic cells in chronic phase (CP) CML patients. Such a mechanism was initially suggested by studies of the effects of enforced expression of p210<sup>BCR–ABL</sup> in immortalised growth factor-dependent cell lines. Autocrine production of IL-3 and GM-CSF was later confirmed in p210<sup>BCR–ABL</sup>-transduced murine bone marrow cells both before and after their transplantation into irradiated mice. It was therefore of interest to determine whether autocrine growth factor production by primary CML cells in patients also increases their levels in the periphery, and if so, how these change with disease progression. We now describe the interesting results of an analysis of serum samples from a large series of CML patients that show stage-specific changes in circulating levels of G-CSF but not IL-3