Erythroid cell development and leukemic transformation: interplay between signal transduction, cell cycle control and oncogenes

Studies using genetically modified mice and ex vivo tissue culture of eryth roid progenitors converge to show that generation of mature erythroid cells depends on the interplay between specific transcriptional regulators and i ntracellular signals controlled by cytokines and growth factors. These stud ies also show that terminal differentiation in the erythroid lineage is unu sual since the acquisition of the phenotypic traits of mature cells occurs while the cells are still actively dividing. Furthermore, under specific st ress conditions, a massive and sustained self-renewal of committed erythroi d progenitors can take place to replenish the pool of terminally differenti ated cells. We review here how the erythroid genetic program and its interp lay with specific cytokines, growth factors and hormones controls survival, proliferation and differentiation of erythroid progenitors both in normal and stress conditions. Special emphasis is laid on our present understandin g of the differences in cell cycle control, which result either in self-ren ewal of erythroid progenitors or in the particular cell divisions which acc ompany terminal differentiation. Finally, we discuss how deregulation of th e various aspects of the physiological control of erythroid progenitor surv ival, proliferation and differentiation can lead to erythroblast transforma tion and erythroleukemia. (C) 2000 Editions scientifiques et medicales Else vier SAS.