Ye Baixin, Sheng Yuping, Zhang Mingming, Hu Yongxian, Huang He
Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 311106, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China; Institute of Hematology, Zhejiang University, Hangzhou, 311112, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, 311112, China.
The First Clinical Medical School, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Cancer Lett. 2022 Jul 10;538:215691. doi: 10.1016/j.canlet.2022.215691. Epub 2022 Apr 23.
Clonal hematopoiesis (CH) is a clonal expansion of single hematopoietic stem cells (HSC) with germline or somatic mutations accumulated in specific genes, which usually leads to clonal dominance via multiple biological pathways and increases the risk of developing hematological malignancies. With the advancement of Next Generation Sequencing (NGS) technology, CH can be widely detected in healthy individuals, many patients complicated with bone marrow failure (BMF), or even in those with myeloproliferative neoplasm (MPN) and therapy-related MDS/AML (t-MDS/AML). Recently, several proof-of-concept studies showed that it is likely to discriminate the CH with high risk developing malignancy through predictive models many years before its onset. Additionally, it has been shown that the CH-related premalignant clones can be abated or eradicated through chemical or genetic measures in animal models, thereby providing an insightful idea for preventing leukemogenesis. However, in despite of these advancements, the clinical implication and early diagnosis of CH for predicting hematological malignancies remain to be more investigated. In this review, we will first review the brief history, risk factors and molecular mechanisms of CH. Then, we will discuss the involved biological process of CH in bone marrow failure diseases, MPN and t-MDS/AML, pointing to its clinical implication. Finally, we will discuss the advancement of early detection of CH at premalignant stage for predicting hematological malignancies, and express perspectives and challenges for early intervention of CH in the future.
克隆性造血（CH）是单个造血干细胞（HSC）的克隆性扩增，其特定基因中积累了种系或体细胞突变，通常通过多种生物学途径导致克隆优势，并增加发生血液系统恶性肿瘤的风险。随着下一代测序（NGS）技术的进步，CH在健康个体、许多合并骨髓衰竭（BMF）的患者甚至骨髓增殖性肿瘤（MPN）和治疗相关的骨髓增生异常综合征/急性髓系白血病（t-MDS/AML）患者中均可广泛检测到。最近，几项概念验证研究表明，通过预测模型有可能在CH发生恶性肿瘤的多年前就对其进行鉴别。此外，研究表明，在动物模型中，与CH相关的癌前克隆可通过化学或基因手段减少或根除，从而为预防白血病发生提供了有见地的思路。然而，尽管有这些进展，CH在预测血液系统恶性肿瘤方面的临床意义和早期诊断仍有待进一步研究。在本综述中，我们将首先回顾CH的简史、危险因素和分子机制。然后，我们将讨论CH在骨髓衰竭疾病、MPN和t-MDS/AML中所涉及的生物学过程，指出其临床意义。最后，我们将讨论在癌前阶段早期检测CH以预测血液系统恶性肿瘤的进展，并表达对未来CH早期干预的观点和挑战。
