DEPENDENCE OF AML PROGENITOR CELLS ON HGFs

LOOD CELLS are derived from small numbers of selfB renewing pluripotent hematopoietic stem cells that reside in the bone marrow and generate progenitor cells committed to proceed along one of the maturation pathways. Because the life span of blood cells is limited, the production rate of blood cells in the marrow is high, even during steadystate conditions. The marrow system has the ability to adapt to sudden changes in the needs of different cell compartments by elevating the production rate of blood cells of specific cell lineages. To satisfy these variable needs, a tight control of the processes of cell renewal, commitment, maturation, and survival for each of the differentiation stages within each blood cell lineage is required. The hematopoietic growth factors (HGFs) play a critical role in regulating these processes. Acute leukemia is characterized by an arrest of maturation and the accumulation of undifferentiated cells in marrow, blood, and other tissues. Similar to normal hematopoiesis, the majority of leukemic cells descend from a relatively small pool of progenitor cells with high proliferative activity. In vitro culture methods used as tools to analyze human leukemia progenitor cells have in recent years been considerably improved as the result of the availability of the recombinant HGFs. We review here current knowledge about the growth properties of acute leukemia progenitor cells derived from the application of in vitro assays. We discuss the significance of these findings in view of the pathogenesis, diagnosis, and treatment of acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL).