ABSTRACT

Normal hematopoiesis is a highly regulated process that occurs in close proximity to the marrow stromal microenvironment. Survival, proliferation, and differentiation of normal hematopoietic progenitors are regulated by interactions with stromal-derived positive and negative regulatory growth factors and with adhesive ligands on stromal cells and stromal extracellular matrix components1,2 (Figure 3.1). Adhesion of normal hematopoietic progenitors to stromal microenvironmental elements is mediated by multiple receptors, including 41 and 51 integrin receptors, CD44, and selectins. Progenitors adhere to cell-surface adhesive ligands such as VCAM-1 and ICAM-1, and extracellular matrix (ECM) components such as fibronectin, thrombospondin, and hyaluronic acid.3-5 In addition to playing a role in anchoring hematopoietic progenitors to appropriate microenvironmental locations and in progenitor migration, homing, and mobilization,6-9 adhesion receptors also play a direct role in the regulation of progenitor growth.10-12

The characteristic features of chronic myeloid leukemia (CML) include abnormal unregulated expansion of malignant BCR/ABL-positive progenitors and precursors as well as premature circulation of malignant progenitors and extramedullary hematopoiesis.13 Abnormalities in adhesive interactions between CML hematopoietic progenitors and the marrow stromal microenvironment may play a role not only in their abnormal circulation but also in their unregulated growth.