Genetic programs of myeloid cell differentiation.

A great body of evidence indicates that hematopoietic cytokines and the availability of their cognate receptors at the cell membrane surface of myeloid progenitors play crucial roles in lineage commitment and differentiation. Little is known of how these receptors couple to downstream signal transduction pathways to convert the extracellular signal into a change in the genetic program. Lineage switching of myeloid progenitors suggests that a limited number of key regulatory genes govern lineage commitment. Several transcription factors have been implicated as key regulators, positive or negative, of myeloid lineage commitment and terminal differentiation. Evidence for an autocrine mechanism involving interleukin-6 in coupling late stages of myeloid cell proliferation to cell maturation is presented. Elucidation of molecular events that take place in cell cycle control associated with growth arrest and differentiation would further enhance the understanding of the genetic programs that govern myeloid cell development.