The effect of granulopoietic stress in mice with "latent" bone marrow failure

Abstract

We treated mice with high-dose busulfan to produce a residual or "latent" hematopoietic injury characterized by persistent normal or near-normal peripheral blood counts and marrow cellularity but moderate to marked reduction in hematopoietic stem cells. Control and "latent" mice were then challenged with glucan, a granulopoietic stimulant. We found that glucan administration induced a comparable increase in granulocytic differentiation in control and "latent" mice. This differentiational expansion was not accompanied by a further depletion of pluripotent hematopoietic stem cells. Our results fail to demonstrate competition between self-renewal and differentiation at the level of the CFUS, at least in this model. Stimuli for granulopoiesis act primarily on more distal, committed populations which are apparently unaffected by prior exposure to busulfan.