Pharmacologic induction of fetal hemoglobin (HbF) is an effective strategy for treating β-hemoglobinopathies like β-thalassemia and sickle cell anemia by ameliorating disease severity. Hydroxyurea is the only FDA-approved agent that induces HbF, but significant nonresponders and toxicity limit its clinical usefulness. This study relates preclinical investigation of Tenofovir disoproxil fumarate (TDF) as a potential HbF inducing agent, using human erythroleukemia cell line and a β-YAC mouse model. Erythroid induction of K562 cells was studied by the benzidine/H₂O₂ reaction, total hemoglobin production was estimated by plasma hemoglobin assay kit, and γ-globin gene expression by RT-qPCR, whereas, fetal hemoglobin production was estimated by flow cytometry and immunofluorescence microscopy. We observed significantly increased γ- globin gene transcription and HbF expression mediated by TDF in K562 cells. Subsequent treatment of β-YAC transgenic mice with TDF confirmed HbF induction in vivo through an increase in γ-globin gene expression and in the percentage of HbF positive red blood cells. Moreover, TDF showed no cytotoxic effect at HbF inducing concentrations. These data support the potential development of TDF for the treatment of hematological disorders, including β-thalassemia and sickle cell anemia.

胎儿血红蛋白（HbF）的药理诱导是通过改善疾病严重程度来治疗β-血红蛋白病（如β地中海贫血和镰状细胞性贫血）的有效策略。羟基脲是唯一获得FDA批准的诱导HbF的药物，但是明显的无反应性和毒性限制了其临床实用性。这项研究涉及使用人类红白血病细胞系和β-YAC小鼠模型对替诺福韦富马酸替诺福韦（TDF）作为潜在的HbF诱导剂进行临床前研究。用联苯胺/ H ₂ O ₂研究类胡萝卜素对K562细胞的诱导作用通过血浆血红蛋白分析试剂盒估计总血红蛋白产量，通过RT-qPCR估计γ-球蛋白基因表达，而通过流式细胞术和免疫荧光显微镜估计胎儿血红蛋白产量。我们观察到由TDF介导的K562细胞中γ-珠蛋白基因转录和HbF表达显着增加。TDF对β-YAC转基因小鼠的后续治疗通过增加γ-球蛋白基因表达和HbF阳性红细胞的百分比证实了体内HbF的诱导。此外，TDF在诱导HbF的浓度下无细胞毒性作用。这些数据支持TDF在治疗血液系统疾病（包括β地中海贫血和镰状细胞性贫血）方面的潜在发展。