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慢性淋巴细胞白血病（ CLL）首次提出疾病中体细胞突变和甲基化改变。这个观点总结了本领域的最新发现和对肿瘤影响。从患者仅有的10％～15％基因突变到低频率相对大范围基因突变，基因组的研究揭示了疾病显著的分子异质性。 NOTCH1和SF3B1突变启动了疾病进展。广泛的基因组研究显示CLL转变和增强子区大范围低甲基化有关。这种表观遗传学程序保留了原始和记忆B细胞起源假设。 CLL表观遗传学和基因组研究为更多个体化诊断和潜在治疗靶点提供了新的前景。“,”Chronic lymphocytic leukemia(CLL) has provided the first comprehensive view of somatic mutations and methylation changes in this disease ,which summarizes the recent findings in this field and the impact on neoplasm.Genomic studies have revealed a remarkable molecular heterogeneity of the disease ,with only few genes mutated in up to 10%-15% of the patients and a relatively large number of genes recurrently mutated at low frequency.NOTCH1 and SF3B1 mutations are emerging as new drivers of aggressive forms of the disease.Genome-wide methylation studies have shown that CLL transformation is associated with a mas-sive hypomethylation phenomenon frequently affecting the enhancer regions .This epigenetic reprogramming maintains an imprint of the putative cell of origin from naive and memory B-cells.Genomic and epigenomic studies of CLL are reshaping our understanding of the disease and provide new perspective for a more individ-ualized diagnosis and new potential therapeutic targets.