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）与髓系肿瘤（MNs）如骨髓增生异常性肿瘤（MDS）和急性髓系白血病（AML）的发病风险增加相关。一般而言，克隆性造血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症（CCUS）。这是一种与年龄相关的现象，其特征是造血干细胞（HSCs）及造血干细胞与祖细胞（HSPCs）中存在体细胞突变，这些突变在选择性压力下获得适应性优势。CHIP患者每年进展为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可能增加治疗相关髓系肿瘤的风险。除血液系统恶性肿瘤外，克隆性造血也是心脏病、脑卒中、慢性阻塞性肺疾病和慢性肾脏病的独立危险因素。诸如克隆性造血风险评分和髓系肿瘤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。针对特定克隆性造血相关突变及特定选择压力的治疗策略，未来可能在克隆性造血及相关疾病的治疗中发挥潜在作用。
Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders
肿瘤(癌症)患者之家