Enumeration of stem cells and progenitor cells in alpha-thalassemic mice reveals lack of specific regulation of stem cell differentiation.

Heterozygous alpha-thalassemic (Hbath/+) female mice were investigated for the effect of persistent erythropoietic stress on the number of stem cells and progenitor cells along the the erythroid (E), granulocyte-macrophage (GM), and megakaryocyte (Meg) pathways. At the progenitor cell level, compensatory erythropoiesis was demonstrated in the spleen but not in the bone marrow. In the spleen, developmentally early progenitor cells (BFU-E) were expanded two- to threefold and late progenitor cells (CFU-E) five- to sixfold. A comparable expansion of progenitor cells was observed along the GM and Meg pathways. CFU-S numbers were increased in the spleen, but not in the bone marrow. The increases in GM and Meg progenitor cells appeared to result in an inappropriate hemopoiesis: peripheral thrombocyte and monocyte numbers were elevated. However, granulocyte numbers were not significantly increased. It is concluded that the persistently increased erythropoietic demand results in inappropriate production of other hemopoietic cells, most likely because pathway-specific regulatory mechanisms do not influence differentiation at the stem cell level.