Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts

Erythropoietin (Epo) controls red cell production in the basal state and du ring stress. Epo binding to its receptor, EpoR, on erythroid progenitors le ads to rapid activation of the transcription factor Stat5. Previously, feta l anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a(-/-)5b(-/-) mice. However, the role of Stat5 in adult eryth ropoiesis was not clear. The present study shows that some adult Stat5a(-/- )5b(-/-) mice have a near-normal hematocrit but are deficient in generating high erythropoletic rates in response to stress. Further, many adult Stat5 a(-/-)5b(-/-) mice have persistent anemia despite a marked compensatory exp ansion in their erythropoletic tissue. Analysis of erythroblast maturation in Stat5a(-/-)5b(-/-) hematopoletic tissue shows a dramatic increase in ear ly erythroblast numbers, but these fail to progress in differentiation. Dec reased expression of bcl-(XL) and increased apoptosis in Stat5a(-/-)5b(-/-) early erythroblasts correlate with the degree of anemia. Hence, Stat5 cont rols a rate-determining step regulating early erythroblast survival. (Blood . 2001;98:3261-3273) (C) 2001 by The American Society of Hematology.