Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
LFKRI, New York Blood Center, New York, United States.
Elife. 2023 Aug 14;12:e90189. doi: 10.7554/eLife.90189.
Erythroblasts possess unique characteristics as they undergo differentiation from hematopoietic stem cells. During terminal erythropoiesis, these cells incorporate large amounts of iron in order to generate hemoglobin and ultimately undergo enucleation to become mature red blood cells, ultimately delivering oxygen in the circulation. Thus, erythropoiesis is a finely tuned, multifaceted process requiring numerous properly timed physiological events to maintain efficient production of 2 million red blood cells per second in steady state. Iron is required for normal functioning in all human cells, the erythropoietic compartment consuming the majority in light of the high iron requirements for hemoglobin synthesis. Recent evidence regarding the crosstalk between erythropoiesis and iron metabolism sheds light on the regulation of iron availability by erythroblasts and the consequences of insufficient as well as excess iron on erythroid lineage proliferation and differentiation. In addition, significant progress has been made in our understanding of dysregulated iron metabolism in various congenital and acquired malignant and non-malignant diseases. Finally, we report several actual as well as theoretical opportunities for translating the recently acquired robust mechanistic understanding of iron metabolism regulation to improve management of patients with disordered erythropoiesis, such as anemia of chronic inflammation, β-thalassemia, polycythemia vera, and myelodysplastic syndromes.
红细胞具有独特的特征，因为它们从造血干细胞分化而来。在终末红细胞生成过程中，这些细胞大量摄取铁以生成血红蛋白，最终进行去核以成为成熟的红细胞，最终在循环中输送氧气。因此，红细胞生成是一个精细调节的、多方面的过程，需要许多适时的生理事件来维持稳态下每秒 200 万个红细胞的高效生成。铁是所有人类细胞正常功能所必需的，鉴于血红蛋白合成对铁的高需求，红细胞生成部分消耗了大部分铁。最近关于红细胞生成和铁代谢之间串扰的证据揭示了红细胞对铁可用性的调节，以及铁不足和过量对红细胞谱系增殖和分化的影响。此外，我们在理解各种先天性和获得性恶性和非恶性疾病中失调的铁代谢方面取得了重大进展。最后，我们报告了几个实际的和理论的机会，以将最近获得的对铁代谢调节的稳健机制理解转化为改善对紊乱的红细胞生成（如慢性炎症性贫血、β-地中海贫血、真性红细胞增多症和骨髓增生异常综合征）患者的管理。
