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

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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Abstract

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.

Methods

To clarify the TPO signal of response in FA, we analyzed FA mice [an1] treated with TPO agonists or crossed with TPO-deficient mice.

Results

Embryonic mice FA fetal liver HSCs were rescued with TPO agonist administration. TPO deficiency no rescued FA FL HSC phenotype.

Conclusions

TPO signal confers developmental FA HSC deficit. Further investigation is needed to describe the mechanism and efficiency.

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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

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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