Zhang Qi, Yim Rita, Lee Paul, Chin Lynn, Li Vivian, Gill Harinder
Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Cancers (Basel). 2024 Dec 9;16(23):4118. doi: 10.3390/cancers16234118.
Clonal hematopoiesis (CH) is associated with an increased risk of developing myeloid neoplasms (MNs) such as myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). In general, CH comprises clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). It is an age-related phenomenon characterized by the presence of somatic mutations in hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells (HSPCs) that acquire a fitness advantage under selection pressure. Individuals with CHIP have an absolute risk of 0.5-1.0% per year for progressing to MDS or AML. Inflammation, smoking, cytotoxic therapy, and radiation can promote the process of clonal expansion and leukemic transformation. Of note, exposure to chemotherapy or radiation for patients with solid tumors or lymphomas can increase the risk of therapy-related MN. Beyond hematological malignancies, CH also serves as an independent risk factor for heart disease, stroke, chronic obstructive pulmonary disease, and chronic kidney disease. Prognostic models such as the CH risk score and MN-prediction models can provide a framework for risk stratification and clinical management of CHIP/CCUS and identify high-risk individuals who may benefit from close surveillance. For CH or related disorders, therapeutic strategies targeting specific CH-associated mutations and specific selection pressure may have a potential role in the future.
克隆性造血（CH）与发生髓系肿瘤（MN）的风险增加相关，如骨髓增生异常综合征（MDS）和急性髓系白血病（AML）。一般来说，CH包括意义未明的克隆性造血（CHIP）和意义未明的克隆性血细胞减少（CCUS）。它是一种与年龄相关的现象，其特征是造血干细胞（HSC）和造血干祖细胞（HSPC）中存在体细胞突变，这些细胞在选择压力下获得适应性优势。CHIP个体每年进展为MDS或AML的绝对风险为0.5-1.0%。炎症、吸烟、细胞毒性治疗和辐射可促进克隆性扩增和白血病转化过程。值得注意的是，实体瘤或淋巴瘤患者接受化疗或放疗会增加治疗相关MN的风险。除血液系统恶性肿瘤外，CH还是心脏病、中风、慢性阻塞性肺疾病和慢性肾脏病的独立危险因素。CH风险评分和MN预测模型等预后模型可为CHIP/CCUS的风险分层和临床管理提供框架，并识别可能受益于密切监测的高危个体。对于CH或相关疾病，针对特定CH相关突变和特定选择压力的治疗策略未来可能具有潜在作用。
