ABSTRACT
This chapter will review what is currently known about the cellular composition of the hematopoietic system of patients with chronic myeloid leukemia (CML) under three major headings: (i) the quantitatively distorted structure of the chronic-phase malignant clone and residual normal cells; (ii) mechanisms responsible for the deregulated hematopoiesis characteristic of chronic-phase disease; (iii) disease progression. As has been the case for all other aspects of CML, significant advances have been made in the last few years in the characterization of the subpopulation of leukemic ‘stem’ cells in CML that initiate and maintain the disease in vivo. These observations have allowed many of the ‘normal’ as well as the ‘abnormal’ features of the leukemic stem cells and their immediate progeny to be identified. At the same time, they have revealed the importance of differentiation-stage-specific perturbations in the turnover and expansion of the leukemic cells in the chronic phase of the disease. This perspective has provided unique clues to the fascinating biology of CML, and offers a framework for explaining the highly variable pathogenesis of the disease in individual patients. Indeed, it seems likely that the eventual successful treatment of CML may well depend on
approaches to patient evaluation and therapy that more fully exploit emerging information about normal and leukemic progenitor cells and their properties.
