Somatic compensation of inherited bone marrow failure

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology Pub Date : 2022-07-01 DOI:10.1053/j.seminhematol.2022.07.002

Sofie Lundgren , Mikko Keränen , Ulla Wartiovaara-Kautto , Mikko Myllymäki

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引用次数: 2

Abstract

Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by insufficient blood cell production and increased risk of transformation to myeloid malignancies. While genetically diverse, IBMFS are collectively defined by a cell-intrinsic hematopoietic stem cell (HSC) fitness defect that impairs HSC self-renewal and hematopoietic differentiation. In IBMFS, HSCs frequently acquire mutations that improve cell fitness, a phenomenon known as somatic compensation. Somatic compensation can occur via distinct genetic processes such as loss of the germline mutation or somatic alterations in pathways affected by the disease-causing gene. While the clinical implications of somatic compensation in IBMFS remain to be fully discovered, understanding these mutational processes can help understand disease pathophysiology and may inform future diagnostic and therapeutic approaches. In this review, we highlight current understanding about somatic compensation in IBMFS.

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遗传性骨髓衰竭的躯体代偿

遗传性骨髓衰竭综合征(IBMFS)是一组异质性遗传疾病，其特征是血细胞生成不足和向髓系恶性肿瘤转化的风险增加。虽然遗传多样性，但IBMFS是由细胞内在造血干细胞(HSC)适应性缺陷共同定义的，这种缺陷会损害HSC的自我更新和造血分化。在IBMFS中，造血干细胞经常获得改善细胞适应性的突变，这种现象被称为体细胞补偿。体细胞补偿可通过不同的遗传过程发生，如种系突变的丧失或受致病基因影响的途径中的体细胞改变。虽然IBMFS中体细胞代偿的临床意义仍有待充分发现，但了解这些突变过程有助于了解疾病病理生理学，并可能为未来的诊断和治疗方法提供信息。在这篇综述中，我们强调了目前对IBMFS的躯体代偿的理解。

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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来源期刊

Seminars in hematology 医学-血液学

CiteScore

6.20

自引率

2.80%

发文量

审稿时长

35 days

期刊介绍： Seminars in Hematology aims to present subjects of current importance in clinical hematology, including related areas of oncology, hematopathology, and blood banking. The journal''s unique issue structure allows for a multi-faceted overview of a single topic via a curated selection of review articles, while also offering a variety of articles that present dynamic and front-line material immediately influencing the field. Seminars in Hematology is devoted to making the important and current work accessible, comprehensible, and valuable to the practicing physician, young investigator, clinical practitioners, and internists/paediatricians with strong interests in blood diseases. Seminars in Hematology publishes original research, reviews, short communications and mini- reviews.