G. Dehaan et al., CONCEPTS OF HEMATOPOIETIC-CELL AMPLIFICATION, SYNERGY, REDUNDANCY ANDPLEIOTROPY OF CYTOKINES AFFECTING THE REGULATION OF ERYTHROPOIESIS, Leukemia & lymphoma, 22(5-6), 1996, pp. 385-394
Hemopoietic cell amplification in vivo is regulated by various mechani
sms which appear to be under control of many hemopoietic growth factor
s. Quiescent stem cells can be activated into cell cycle, dividing pro
genitor cells can reduce their cell cycle time, the differentiation ve
locity (i.e. transit-time) can be manipulated, apoptosis can be preven
ted, and finally, at least in the murine system, migration of cells be
tween the microenvironments in marrow and spleen may take place. Pertu
rbations of any of the parameters by which these mechanisms are define
d, will affect in vivo blood cell production. In this review the conse
quences of these perturbations, and the role of growth factors herein,
are discussed. These fundamental aspects of the regulation of hemopoi
esis are illustrated with recent data showing the synergistic, redunda
nt and pleiotropic effects of SCF, IL-11, EPO and G-CSF on the in vivo
formation of erythrocytes. Given the overwhelming number of growth fa
ctor-related studies that are now appearing, a re-evaluation of data,
available in the literature, in the context of the mechanistic approac
h of growth factor-dependent hemopoiesis which is presented in this pa
per, seems to be useful and warranted.