1st Department of Medicine, Department of Hematology, General University Hospital, U Nemocnice 2, Prague 2, 128 00, Czech Republic.
Ann Hematol. 2013 Jan;92(1):11-8. doi: 10.1007/s00277-012-1568-1. Epub 2012 Sep 11.
Friend leukemia virus integration 1 (Fli1) and erythroid Krüppel-like factor (EKLF) participate under experimental conditions in the differentiation of megakaryocytic and erythroid progenitor in cooperation with other transcription factors, cytokines, cytokine receptors, and microRNAs. Defective erythropoiesis with refractory anemia and effective megakaryopoiesis with normal or increased platelet count is typical for 5q- syndrome. We decided to evaluate the roles of EKLF and Fli1 in the pathogenesis of this syndrome and of another ribosomopathy, Diamond-Blackfan anemia (DBA). Fli1 and EKLF mRNA levels were examined in mononuclear blood and bone marrow cells from patients with 5q- syndrome, low-risk MDS patients with normal chromosome 5, DBA patients, and healthy controls. In 5q- syndrome, high Fli1 mRNA levels in the blood and bone marrow mononuclear cells were found. In DBA, Fli1 expression did not differ from the controls. EKLF mRNA level was significantly decreased in the blood and bone marrow of 5q- syndrome and in all DBA patients. We propose that the elevated Fli1 in 5q- syndrome protects megakaryocytic cells from ribosomal stress contrary to erythroid cells and contributes to effective though dysplastic megakaryopoiesis.
Friend 白血病病毒整合 1 (Fli1) 和红细胞 Krüppel 样因子 (EKLF) 在实验条件下与其他转录因子、细胞因子、细胞因子受体和 microRNAs 一起参与巨核细胞和红细胞祖细胞的分化。5q- 综合征的典型特征是无效性红细胞生成伴难治性贫血和有效巨核细胞生成伴正常或增加的血小板计数。我们决定评估 EKLF 和 Fli1 在该综合征和另一种核糖体病 Diamond-Blackfan 贫血 (DBA) 的发病机制中的作用。检测了 5q- 综合征、染色体 5 正常的低危 MDS 患者、DBA 患者和健康对照者的单核血和骨髓细胞中的 Fli1 和 EKLF mRNA 水平。在 5q- 综合征中，发现血液和骨髓单核细胞中的 Fli1 mRNA 水平升高。在 DBA 中，Fli1 表达与对照组无差异。5q- 综合征和所有 DBA 患者的血液和骨髓中的 EKLF mRNA 水平均显著降低。我们提出，升高的 Fli1 在 5q- 综合征中保护巨核细胞免受核糖体应激，与红细胞相反，并有助于有效但发育不良的巨核细胞生成。
