The influence of growth regulation on treatment strategy for acute myeloblastic leukaemia.

Acute myeloblastic leukaemia (AML) is a useful model for generalized malignant disease. Haemopoiesis in AML is clonal; a characteristic cell population (blast cells) has been identified and can be grown in culture. The population is organized as a hierarchy, headed by self-renewing stem cells. Several control mechanisms affect the behaviour of these stem cells. Two classes of regulatory receptors are identified that act by ligand-receptor interaction; in one class the receptors are intracellular, in the other they are in the cell membrane. It is proposed that the many regulatory signals received by blast cells contribute to a genetically determined regulatory milieu that sets the probabilities of blast stem cell renewal and differentiation. Interactions have been identified between regulatory mechanisms and the responses of blast stem cells to chemotherapeutic agents. It is suggested that new therapeutic options are emerging, based on the exploitation of regulatory mechanisms in conjunction with chemotherapy.