正常造血干细胞和白血病干细胞的休眠调节,The FEBS Journal

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正常造血干细胞和白血病干细胞的休眠调节
The FEBS Journal ( IF 5.5 ) Pub Date : 2022-05-05 , DOI: 10.1111/febs.16472
Kristbjorn Orri Gudmundsson ₁ , Yang Du ₂

Affiliation

造血系统由稀有的造血干细胞 (HSC) 维持，这些细胞大部分时间处于静止状态，仅偶尔分裂以进行自我更新和/或通过产生高度增殖的祖细胞进行克隆扩张。后者负责通过随后的谱系定型和终末分化产生系统的所有成熟细胞。具有类似特性的细胞也存在于白血病中，被称为白血病干细胞（LSC）。静止为 HSC 和 LSC 提供必要的保护，使其免受细胞毒性应激和 DNA 损伤，并且就 LSC 而言，可能会导致白血病患者出现治疗抵抗和疾病复发。特异性抑制 LSC 静止被认为是消除 LSC 和治愈白血病的有前途的策略。尽管对这些细胞中负责维持静止的机制的理解仍然有限，特别是对于 LSC，但最近的研究表明它们对某些途径的依赖性以及它们因循环增加而引起的应激和 DNA 损伤水平存在潜在差异。这种差异可能源于 LSC 的致癌突变，并且可以专门用于消除 LSC，同时在未来保留正常的 HSC。

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Quiescence regulation by normal haematopoietic stem cells and leukaemia stem cells

The haematopoietic system is maintained by rare haematopoietic stem cells (HSCs), which are quiescent most of the time and only divide occasionally to self-renew and/or to undergo commitment to clonal expansion via the generation of highly proliferative progenitor cells. The latter is responsible for the generation of all mature cells of the system through subsequent lineage commitment and terminal differentiation. Cells with similar properties also exist in leukaemias and are known as leukaemia stem cells (LSCs). Quiescence provides essential protection for both HSC and LSC from cytotoxic stress and DNA damage and, in the case of LSCs, likely causes therapy resistance and disease relapse in leukaemia patients. Specific inhibition of LSC quiescence has been considered a promising strategy for eliminating LSCs and curing leukaemias. Although the understanding of mechanisms responsible for quiescence maintenance in these cells remains limited, particularly for LSCs, recent studies have suggested potential differences in their dependency on certain pathways and their levels of stress and DNA damage caused by increased cycling. Such differences likely stem from oncogenic mutations in LSCs and could be specifically exploited for the elimination of LSCs while sparing normal HSCs in the future.

更新日期：2022-05-05

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