Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in β-thalassemia

摘要: In beta-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by beta-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized limited cell differentiation. thalassemic mice, observed that greater than normal percentage was S-phase, exhibiting an erythroblast-like morphology. Thalassemic were associated expression cycle-promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, Ki-67 antiapoptotic protein Bcl-X(L). The differentiated less ones vitro. To investigate Jak2 responsible for differentiation, administered inhibitor, TG101209, Exposure TG101209 dramatically decreased spleen size but anemia. Although our data do not exclude role IE, propose expansion pool followed differentiation exacerbates thalassemia. addition, these results suggest use inhibitors has potential profoundly change management this disorder.