Capelletti Martina Maria, Montini Orsola, Ruini Emilio, Tettamanti Sarah, Savino Angela Maria, Sarno Jolanda
School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy.
Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy.
Int J Mol Sci. 2024 Dec 24;26(1):45. doi: 10.3390/ijms26010045.
Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Understanding the metabolic diversities among cancer cells and their surrounding environments is therefore essential in unravelling the complexities of leukaemia and improving therapeutic strategies. Here, we describe the currently available methodologies and approaches to addressing the dynamic heterogeneity of leukaemia progression. In the second section, we focus on metabolic leukaemic vulnerabilities in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Lastly, we provide a comprehensive overview of the most interesting clinical trials designed to target these metabolic dependencies, highlighting their potential to advance therapeutic strategies in leukaemia treatment. The integration of multi-omics data for cancer identification with the metabolic states of tumour cells will enable a comprehensive "micro-to-macro" approach for the refinement of clinical practices and delivery of personalised therapies.
血液系统癌症的遗传学研究指出白血病在不同亚群中存在异质性，具有不同的突变和特征，影响治疗反应。新一代测序（NGS）、全基因组分析以及单细胞技术，为深入了解同一肿瘤内的克隆异质性提供了前所未有的视角。这种异质性中一个尚未被探索的关键组成部分是细胞内代谢组，它是一个决定细胞功能、信号传导、表观基因组调控、免疫和炎症的动态网络。因此，了解癌细胞与其周围环境之间的代谢多样性对于揭示白血病的复杂性和改进治疗策略至关重要。在这里，我们描述了目前用于解决白血病进展动态异质性的方法和途径。在第二部分中，我们重点关注急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）中的代谢性白血病脆弱性。最后，我们全面概述了旨在针对这些代谢依赖性的最有趣的临床试验，强调它们在推进白血病治疗策略方面的潜力。将用于癌症识别的多组学数据与肿瘤细胞的代谢状态相结合，将实现一种全面的“微观到宏观”方法，以完善临床实践并提供个性化治疗。
