Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the clonal expansion of abnormal lymphoid precursors in bone marrow, which leads to alterations in the processes of cell differentiation and maturation as a consequence of genetic alterations. The integration of conventional methods, such as cytogenetics and immunophenotyping, and next-generation sequencing (NGS) has led to significant improvements at diagnosis and patient stratification; this has also allowed the discovery of several novel molecular entities with specific genetic variants that may drive the processes of leukemogenesis. Nevertheless, the understanding of the process of leukemogenesis remains a challenge since this disease persists as the most frequent cancer in children; it accounts for approximately one-quarter of adult acute leukemias, and the patient management may take into consideration the high intra- and inter-tumor heterogeneity and the relapse risk due to the various molecular events that can occur during clonal evolution. Some germline variants have been identified as risk factors or have been found to be related to the response to treatment. Therefore, better knowledge of the genetic alterations in B-ALL will have a prognostic impact from the perspective of personalized medicine. This review aims to compare, synthesize, and highlight recent findings concerning ALL obtained through NGS that have led to a better understanding of new molecular subtypes based on immunophenotypic characteristics, mutational profiles, and expression profiles.
急性淋巴细胞白血病（ALL）是一种血液系统恶性肿瘤，其特征是骨髓中异常淋巴前体细胞的克隆性扩增，这种扩增由遗传改变引起，进而导致细胞分化和成熟过程发生异常。传统方法（如细胞遗传学和免疫表型分析）与新一代测序（NGS）技术的结合，显著改善了该疾病的诊断和患者分层；同时也发现了多种具有特定遗传变异的新型分子实体，这些变异可能驱动白血病的发生过程。然而，对该疾病发生机制的理解仍面临挑战，因为ALL在儿童中仍是最常见的癌症类型，约占成人急性白血病的四分之一。在患者管理过程中，需充分考虑肿瘤内部及肿瘤间的高度异质性，以及克隆进化过程中可能发生的多种分子事件导致的复发风险。一些胚系变异已被确定为风险因素，或被发现与治疗反应相关。因此，从个体化医疗的角度来看，更深入地了解B-ALL的遗传改变将具有重要的预后意义。本综述旨在比较、综合并重点阐述通过NGS技术获得的ALL最新研究成果，这些成果基于免疫表型特征、突变谱和表达谱，促进了对新型分子亚型的深入理解。
Unraveling the Genetic Heterogeneity of Acute Lymphoblastic Leukemia Based on NGS Applications
肿瘤(癌症)患者之家