Ingley Evan, McCarthy David J, Pore Jessica R, Sarna Mohinda K, Adenan Aini S, Wright Michael J, Erber Wendy, Tilbrook Peta A, Klinken S Peter
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, WA, Australia.
Oncogene. 2005 Jan 13;24(3):336-43. doi: 10.1038/sj.onc.1208199.
In vitro studies have implicated the Lyn tyrosine kinase in erythropoietin signaling. In this study, we show that J2E erythroid cells lacking Lyn have impaired signaling and reduced levels of transcription factors STAT5a, EKLF and GATA-1. Since mice lacking STAT5, EKLF or GATA-1 have red cell abnormalities, this study also examined the erythroid compartment of Lyn(-/-) mice. Significantly, STAT5, EKLF and GATA-1 levels were appreciably lower in Lyn(-/-) erythroblasts, and the phenotype of Lyn(-/-) animals was remarkably similar to GATA-1(low) animals. Although young adult Lyn-deficient mice had normal hematocrits, older mice developed anemia. Grossly enlarged erythroblasts and florid erythrophagocytosis were detected in the bone marrow of mice lacking Lyn. Markedly elevated erythroid progenitors and precursor levels were observed in the spleens, but not bone marrow, of Lyn(-/-) animals indicating that extramedullary erythropoiesis was occurring. These data indicate that Lyn(-/-) mice display extramedullary stress erythropoiesis to compensate for intrinsic and extrinsic erythroid defects.
体外研究表明Lyn酪氨酸激酶参与促红细胞生成素信号传导。在本研究中，我们发现缺乏Lyn的J2E红系细胞信号传导受损，转录因子STAT5a、EKLF和GATA-1水平降低。由于缺乏STAT5、EKLF或GATA-1的小鼠存在红细胞异常，本研究还检查了Lyn(-/-)小鼠的红系细胞区室。值得注意的是，Lyn(-/-)成红细胞中STAT5、EKLF和GATA-1水平明显较低，Lyn(-/-)动物的表型与GATA-1(low)动物非常相似。虽然年轻的成年Lyn缺陷小鼠血细胞比容正常，但老年小鼠会出现贫血。在缺乏Lyn的小鼠骨髓中检测到明显肿大的成红细胞和大量红细胞吞噬现象。在Lyn(-/-)动物的脾脏而非骨髓中观察到红系祖细胞和前体细胞水平显著升高，表明正在发生髓外造血。这些数据表明，Lyn(-/-)小鼠表现出髓外应激造血以补偿内在和外在的红系缺陷。
