Genetically determined regulators acting on the blast cells of acute myeloblastic leukemia

Regulatory mechanisms affecting the growth of leukemic cells are attractive targets for new treatments. The blast cells of acute myeloblastic leukemia (AML) may be considered as a lineage; a minority are stem cells capable of both self-renewal and determination followed by terminal divisions ending in proliferatively inert cells retaining blast morphology. Two cell culture methods are available for the study of blasts. The first is a clonogenic assay. Blast stem cells form colonies in methylcellulose, containing proliferatively inert blast cells, together with a small number of new progenitors. Growth factor(s) are usually required. These may be supplied by media conditioned by the continuous bladder carcinoma cell line HTB9 (HTB9-CM). The recombinant growth factors GM-CSF and G-CSF are also active, and in many instances are synergistic. Blast progenitors will also grow in suspension, provided the cell density is high and growth factors are provided. In these cultures, blast progenitors increase in number, reflecting their self-renewal capacity. Evidence is also available that specific genes may be involved in the self-renewal process. Thus, three forms of growth regulation, similar to those encoded by proto-oncogenes, can be shown to be operative in AML blast cell cultures.