Leukemia and the disruption of normal hematopoiesis

The goal of this review is to highlight recent advances in our understanding of the pathobiology of leukemias and lymphomas. Our theme throughout will be to relate specific mechanisms involved in the initiation and progression of leukemia to the alteration of the normal homeostatic mechanisms used to regulate the production of blood cells. Advances in the definition of hematopoietic growth factors and their receptors and cellular oncogenes provide a reservoir of possibilities to consider for growth deregulation. When possible we will concentrate on mechanisms defined for human leukemias and lymphomas and use data from experimental animal models for contrast or to demonstrate unique concepts. Although many of the points we will describe could relate to most leukemias (e.g., clonality, or block to differentiation), we have chosen specific leukemias or lymphomas to exemplify such concepts. Advancement in the isolation and characterization of the pluripotent stem cell has furthered our understanding of its related malignancies. Most leukemias, however, have classically been categorized as lymphoid or myeloid (Figure 1). We have favored grouping hematopoietic neoplasias according to related molecular and cell biologic mechanisms. We will discuss selected examples that appear to function as regulators of cell growth or differentiation. We define leukemia as the uncontrolled proliferation