Model for Stat5a^−/−5b^−/− erythropoiesis.

Erythroid progenitors vary in their sensitivity to apoptosis and in their requirements for antiapoptotic signaling from EpoR.34 Under conditions of maximal erythropoietic rate, during rapid growth or in response to stress, all erythroid progenitors are rescued from apoptosis and give rise to red cells (left-hand panel). Impairment of EpoR antiapoptotic signaling in Stat5a^−/−5b^−/− neonates under rapid growth conditions will lead to apoptosis of the more sensitive progenitors and result in developmental anemia (middle panel). Surviving Stat5a^−/−5b^−/− adults are able to partly compensate for the deficit in EpoR antiapoptotic signaling by increasing the size of the early erythroblast population. This may result in improved rates of red cell production at the expense of expanded erythropoietic tissue and increased apoptosis (right-hand panel).