急性淋巴细胞白血病（ALL）是儿童中最常见的癌症。 ALL 起源于前体淋巴细胞，随着时间的推移，前体淋巴细胞会发生多种基因组变化，包括染色体重排和点突变。虽然在过去 30 年里，人们在 ALL 中发现并描述了多种基因组缺陷，但直到最近几年，克隆异质性才被认识到。由于单细胞测序技术的最新进展，已经从分析数百个细胞发展到同时分析数千个细胞，肿瘤异质性的研究现在成为可能。可以在单细胞水平上探索不同的模式：DNA、RNA、表观遗传修饰以及细胞内和细胞表面蛋白。在这篇综述中，我们描述了这些技术并强调了它们在 ALL 生物学研究中的优点和局限性。此外，多组学技术和空间维度的结合可以提供对细胞间通讯的深入了解。我们描述了不同的单细胞测序技术如何帮助揭示 ALL 的分子复杂性，揭示其发展、异质性、其与白血病微环境的相互作用以及可能的复发机制。© 2024。作者，独家向 Springer Nature Switzerland AG 授予许可。

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL originates from precursor lymphocytes that acquire multiple genomic changes over time, including chromosomal rearrangements and point mutations. While a large variety of genomic defects was identified and characterized in ALL over the past 30 years, it was only in recent years that the clonal heterogeneity was recognized. Thanks to the latest advancements in single-cell sequencing techniques, which have evolved from the analysis of a few hundred cells to the analysis of thousands of cells simultaneously, the study of tumor heterogeneity now becomes possible. Different modalities can be explored at the single-cell level: DNA, RNA, epigenetic modifications, and intracellular and cell surface proteins. In this review, we describe these techniques and highlight their advantages and limitations in the study of ALL biology. Moreover, multiomics technologies and the incorporation of the spatial dimension can provide insight into intercellular communication. We describe how the different single-cell sequencing technologies help to unravel the molecular complexity of ALL, shedding light on its development, its heterogeneity, its interaction with the leukemia microenvironment and possible relapse mechanisms.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.