Scholarlink

<p>Zinc finger and BTB domain-containing 7A (ZBTB7A) is a transcription factor repressor of fetal hemoglobin (HbF; α<sub>2</sub>γ<sub>2</sub>) in erythroid cells. Reactivating γ-globin expression represents a promising therapeutic strategy for β-hemoglobinopathies, including β-thalassemia. While <i>ZBTB7A</i> knockdown is known to elevate HbF levels in HUDEP-2 erythroid cell line and human hematopoietic stem/progenitor cell (HSPC)-derived erythroblasts, its effects in patient-derived cells remain less defined. This study investigates the effects of <i>ZBTB7A</i> downregulation in erythroid cells derived from both β<sup>0</sup> thalassemia/hemoglobin E (β<sup>0</sup>-thal/HbE) patients and healthy donors. ZBTB7A knockdown upregulated embryonic and fetal globin genes (ε-, ζ-, γ-globin), and robust HbF induction while suppressing adult globin gene expression (α-, β-, δ-globin) in both groups. Notably, partial <i>ZBTB7A</i> inhibition was sufficient to achieve HbF reactivation. ZBTB7A depletion delayed erythroid maturation in healthy cells, but not in β⁰-thal/HbE cells, revealing a context-dependent effect on differentiation. These findings support ZBTB7A as a compelling target for β-thalassemia therapy, where partial inhibition could potentially offer therapeutic benefit while minimizing adverse effects on erythroid differentiation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Downregulation of ZBTB7A/LRF increases fetal hemoglobin expression in β0-thalassemia/hemoglobin E erythroid cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月5日

查看全文
  • Sukanya Chumchuen,
  • Tanapat Pornsukjantra,
  • Pawarit Innachai,
  • Pinyaphat Khamphikham,
  • Chokdee Wongborisuth,
  • Usanarat Anurathapan,
  • Duantida Songdej,
  • Orapan Sripichai,
  • Amornrat Tangprasittipap,
  • Suradej Hongeng

摘要

Zinc finger and BTB domain-containing 7A (ZBTB7A) is a transcription factor repressor of fetal hemoglobin (HbF; α2γ2) in erythroid cells. Reactivating γ-globin expression represents a promising therapeutic strategy for β-hemoglobinopathies, including β-thalassemia. While ZBTB7A knockdown is known to elevate HbF levels in HUDEP-2 erythroid cell line and human hematopoietic stem/progenitor cell (HSPC)-derived erythroblasts, its effects in patient-derived cells remain less defined. This study investigates the effects of ZBTB7A downregulation in erythroid cells derived from both β0 thalassemia/hemoglobin E (β0-thal/HbE) patients and healthy donors. ZBTB7A knockdown upregulated embryonic and fetal globin genes (ε-, ζ-, γ-globin), and robust HbF induction while suppressing adult globin gene expression (α-, β-, δ-globin) in both groups. Notably, partial ZBTB7A inhibition was sufficient to achieve HbF reactivation. ZBTB7A depletion delayed erythroid maturation in healthy cells, but not in β⁰-thal/HbE cells, revealing a context-dependent effect on differentiation. These findings support ZBTB7A as a compelling target for β-thalassemia therapy, where partial inhibition could potentially offer therapeutic benefit while minimizing adverse effects on erythroid differentiation.