Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders

IF 2.7 3区医学 Q2 HEMATOLOGY

Current Hematologic Malignancy Reports Pub Date : 2023-12-14 DOI:10.1007/s11899-023-00719-2

Terra Lasho, Mrinal M. Patnaik

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Abstract

Purpose of Review

Telomere biology disorders (TBDs) are germline-inherited conditions characterized by reduction in telomerase function, accelerated shortening of telomeres, predisposition to organ-failure syndromes, and increased risk of neoplasms, especially myeloid malignancies. In normal cells, critically short telomeres trigger apoptosis and/or cellular senescence. However, the evolutionary mechanism by which TBD-related telomerase-deficient cells can overcome this fitness constraint remains elusive.

Recent Findings

Preliminary data suggests the existence of adaptive somatic mosaic states characterized by variants in TBD-related genes and maladaptive somatic mosaic states that attempt to overcome hematopoietic fitness constraints by alternative methods leading to clonal hematopoiesis.

Summary

TBDs are both rare and highly heterogeneous in presentation, and the association of TBD with malignant transformation is unclear. Understanding the clonal complexity and mechanisms behind TBD-associated molecular signatures that lead to somatic adaptation in the setting of defective hematopoiesis will help inform therapy and treatment for this set of diseases.

Abstract Image

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端粒生物学疾病中的适应性和不适应性克隆造血

端粒生物学疾病(tbd)是种系遗传疾病，其特征是端粒酶功能降低，端粒加速缩短，易患器官衰竭综合征，肿瘤，特别是髓系恶性肿瘤的风险增加。在正常细胞中，极短的端粒触发细胞凋亡和/或细胞衰老。然而，与tbd相关的端粒酶缺陷细胞克服这种适应性限制的进化机制仍然难以捉摸。最近的发现初步数据表明，存在以tbd相关基因变异为特征的适应性体细胞镶嵌状态和试图通过替代方法克服造血适应性限制的非适应性体细胞镶嵌状态，从而导致克隆造血。TBD既罕见又具有高度异质性，其与恶性转化的关系尚不清楚。了解克隆复杂性和tbd相关分子特征背后的机制，这些分子特征导致造血缺陷的躯体适应，将有助于为这组疾病的治疗提供信息。

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来源期刊

Current Hematologic Malignancy Reports ONCOLOGY-HEMATOLOGY

CiteScore

6.00

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： his journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of hematologic malignancy. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as leukemia, lymphoma, myeloma, and T-cell and other lymphoproliferative malignancies. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.