TPO激动剂挽救遗传性骨髓衰竭综合征中的造血干细胞发育

IF 0.7 Q4 HEMATOLOGY

Leukemia Research Reports Pub Date : 2024-01-01 DOI:10.1016/j.lrr.2024.100438

M. Mochizuki, A. Nakamura-Ishizu

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引用次数: 0

摘要

导言范可尼贫血（FA）基因是一种先天性骨髓衰竭（BMF）疾病，由与 DNA 损伤修复相关的复制应激（RS）受损引起。我们先前描述了FA胎儿肝脏（FL）造血干细胞（HSC）在RS作用下表现出高线粒体氧化磷酸化（OXPHOS）和有丝分裂。众所周知，血小板生成素（TPO）信号可调节造血干细胞线粒体的新陈代谢。为了明确TPO信号在FA中的反应，我们分析了用TPO激动剂治疗或与TPO缺陷小鼠杂交的FA小鼠[an1]。结论 TPO 信号导致发育期 FA 胎儿肝脏造血干细胞缺失。需要进一步研究其机制和效率。

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TPO AGONIST RESCUED DEVELOPMENTAL HEMATOPOIETIC STEM CELL IN HEREDITARY BONE MARROW FAILURE SYNDROME

Introduction

Fanconi Anemia (FA) gene is a congenital bone marrow failure (BMF) disorder caused by impaired replication stress (RS) associated DNA damage repair. We previously described FA fetal liver (FL) hematopoietic stem cell (HSC) exhibited high mitochondrial oxidative phosphorylation (OXPHOS) and mitophagy when it was under RS. Thrombopoietin (TPO) signaling is known to modulate mitochondria metabolism in HSC. While TPO agonists are utilized for the treatment of BMFs such as aplastic anemia, whether and how these drugs can affect FA and its progression to hematopoietic malignancy is unknown.