Hematopoietic growth factors and in vitro growth of human acute myeloblastic leukemia.

The production of mature blood cells is finely regulated, so that the homeostasis can be maintained and cell production be adapted to the specific needs of particular blood cell compartments (e.g., granulocytes during infection). A complex regulatory network of positive and negative signals and cellular interactions serves the hematopoietic system to fulfill this role. In vitro colony assays are powerful tools for studies that aim at the recognition of hematopoietic progenitor cells of distinct differentiation pathways and at different levels of maturation. These assays have also been used to define the complex role of hematopoietic growth factors in normal hematopoiesis. The same technology is currently being applied for elucidating growth factor responses of neoplastic clonogenic cells in hematopoietic disease. An in vitro colony assay for primitive multilineage hematopoietic precursor cells of both rodents and humans with the capacity to form granulocytic cells, macrophages, erythrocytes, megakaryocytes, collectively designated as CFUGEMM, has been developed. I-3 Somewhat more mature progenitor cells that are committed to one hematopoietic lineage can be assayed in vitro as erythroid burst-forming units (BFUE),4.5 erythroid colony-forming units (CFU-E),6 granulocyte/ monocyte CFU (CFU-GM),7.8 granulocyte CFU (CFU-G), monocyte CFU (CFU-M), eosinophil CFU (CFU-Eo), or megakaryocyte CFU (CFU-Mega).’ Several regulatory molecules that induce colony formation from those precursor cells have been isolated following molecular cloning. In acute myeloid leukemia (AML), a transformed malignant precursor cell arises that is unable to generate terminally differentiated cells. This neoplastic cell population apparently escapes normal maturation impulses and expands aproportionally in marrow and blood. The technology of in vitro colony formation has been applied to examine the proliferation and differentiation abilities of leukemic progenitor cells. In this review we discuss our understanding of leukemic blood cell formation in human AML, mainly based on the study of in vitro growth.