使用超极化 13C NMR 根据代谢特征区分白血病亚型。
Differentiating leukemia subtypes based on metabolic signatures using hyperpolarized 13C NMR.
发表日期:2024 Sep 25
作者:
Nichlas Vous Christensen, Christoffer Laustsen, Lotte Bonde Bertelsen
来源:
NMR IN BIOMEDICINE
摘要:
白血病是一组血癌,分为四大类。在这四个类别中,存在许多不同的亚型,它们具有相似的起源、基因突变和成熟水平,这使得它们难以区分。尽管它们有相似之处,但它们对治疗的反应可能不同,因此区分它们至关重要。紊乱的代谢表型(瓦尔堡效应)经常出现在癌细胞(包括白血病细胞)中,并且越来越成为改进诊断和治疗的目标。在本研究中,使用超极化 13C NMR 光谱来表征六种白血病细胞系 ML-1、CCRF-CEM、THP-1、MOLT-4、HL-60 和 K562 的代谢特征。这是使用[1-13C]丙酮酸和[1-13C]丙氨酸作为生物探针,对经过和未经2-脱氧-D-葡萄糖处理的培养细胞进行下游代谢物定量和动力学分析来完成的。类似白血病亚型的代谢特征可以很容易地区分。这包括ML-1和THP-1,它们属于相似的M4和M5 AML亚型,CCRF-CEM和MOLT-4,它们在不同成熟状态下属于相似的T-ALL谱系,以及HL-60和K562,它们属于密切相关的 M1 和 M2 AML 亚型。这里提供的数据证明了超极化 13C NMR 波谱作为区分相似起源的白血病亚型的方法的潜力。将此方法与生物反应器设置相结合可能会实现更好的白血病疾病管理,因为可以通过重复实验和干预从单次活检中获取代谢特征。© 2024 作者。约翰·威利 (John Wiley) 出版的《生物医学中的核磁共振》
Leukemia is a group of blood cancers that are classified in four major classes. Within these four classes, many different subtypes exists with similar origin, genetic mutations, and level of maturity, which can make them difficult to distinguish. Despite their similarities, they might respond differently to treatment, and therefore distinguishing between them is of crucial importance. A deranged metabolic phenotype (Warburg effect) is often seen in cancer cells, leukemia cells included, and is increasingly a target for improved diagnosis and treatment. In this study, hyperpolarized 13C NMR spectroscopy was used to characterize the metabolic signatures of the six leukemia cell lines ML-1, CCRF-CEM, THP-1, MOLT-4, HL-60, and K562. This was done using [1-13C]pyruvate and [1-13C]alanine as bioprobes for downstream metabolite quantification and kinetic analysis on cultured cells with and without 2-deoxy-D-glucose treatment. The metabolic signatures of similar leukemia subtypes could be readily distinguished. This includes ML-1 and THP-1, which are of the similar M4 and M5 AML subtypes, CCRF-CEM and MOLT-4, which are of the similar T-ALL lineage at different maturation states, and HL-60 and K562, which are of the closely related M1 and M2 AML subtypes. The data presented here demonstrate the potential of hyperpolarized 13C NMR spectroscopy as a method to differentiate between leukemia subtypes of similar origin. Combining this method with bioreactor setups could potentially allow for better leukemia disease management as metabolic signatures could be acquired from a single biopsy through repeated experimentation and intervention.© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.