Chronic lymphocytic leukaemia (CLL), the most frequent type of leukaemia in adults, is a lymphoproliferative disorder that is characterized by the expansion of monoclonal, mature CD5⁺CD23⁺ B cells in the peripheral blood, secondary lymphoid tissues and bone marrow. CLL is an incurable disease with a heterogeneous clinical course, for which the treatment decision still relies on conventional parameters (such as clinical stage and lymphocyte doubling time). During the past 5 years, relevant advances have been made in understanding CLL biology. Indeed, substantial progress has been made in the identification of the putative cell of origin of CLL, and comprehensive studies have dissected the genomic, epigenomic and transcriptomic landscape of CLL. Advances in clinical management include improvements in our understanding of the prognostic value of different genetic lesions, particularly those associated with chemoresistance and progression to highly aggressive forms of CLL, and the advent of new therapies targeting crucial biological pathways. In this Review, we discuss new insights into the genetic lesions involved in the pathogenesis of CLL and how these genetic insights influence clinical management and the development of new therapeutic strategies for this disease.

慢性淋巴细胞白血病 (CLL) 是成人最常见的白血病类型，是一种淋巴细胞增殖性疾病，其特征是单克隆成熟 CD5 ⁺ CD23 ⁺外周血、次级淋巴组织和骨髓中的 B 细胞。CLL是一种临床病程异质性的不治之症，其治疗决策仍依赖于常规参数（如临床分期和淋巴细胞倍增时间）。在过去 5 年中，在理解 CLL 生物学方面取得了相关进展。事实上，在识别假定的 CLL 起源细胞方面已经取得了实质性进展，综合研究已经剖析了 CLL 的基因组、表观基因组和转录组学格局。临床管理的进步包括我们对不同遗传病变预后价值的理解的提高，特别是那些与化学抗性和进展为高度侵袭性 CLL 相关的病变，以及针对关键生物途径的新疗法的出现。在这篇综述中，我们讨论了对涉及 CLL 发病机制的遗传病变的新见解，以及这些遗传见解如何影响临床管理和该疾病新治疗策略的开发。