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急性髓系白血病中的微生物代谢组学:从发病机制到治疗

Microbial metabolomics in acute myeloid leukemia: From pathogenesis to treatment.

作者信息

Nowicka Aneta, Gil Lidia

机构信息

Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poland.

出版信息

Adv Clin Exp Med. 2025 Jul;34(7):1201-1212. doi: 10.17219/acem/191559.

Abstract

Acute myeloid leukemia (AML), the most common leukemia in adults, is a biologically heterogeneous disease arising from clonally proliferating hematopoietic stem cells. Increased appreciation of novel genetic methods has improved the understanding of AML biology. Recently, the emerging field of metabolomics has indicated qualitative and quantitative alterations in metabolic profiles in AML pathogenesis, progression and treatment. Multiple metabolic and molecular pathways regulate human metabolism and host-microbiome interactions may significantly affect this biochemical machinery. Microbiota have been found to play a significant role in hematopoietic function, metabolism and immunity, contributing to AML occurrence. A large number of studies have highlighted the importance of the composition and diversity of the gut microbiota (GM) in response to treatment and prognosis in AML. Moreover, strong evidence emphasizes the detrimental link between dysbiosis and infectious complications, a leading cause of morbidity and mortality for patients with AML. Several microbiota-related mechanisms have been linked to particular changes in host physiology so far, and microbial-derived metabolites belong to one of the most important. Circulating in the body, they modulate human conditions both locally and systemically. The extensive and diverse repertoire of bacterial metabolic functions plays a critical role in numerous processes, including leukemogenesis. Integrative analysis of microbiome and metabolome data is a promising avenue for better understanding the complex relationship between the microbiota, biochemical alterations and AML pathogenesis to effectively prevent, treat and mitigate its outcomes. This review concentrates on the pathologic roles and therapeutic implications of microbe-derived metabolites in AML settings.

摘要

急性髓系白血病(AML)是成人中最常见的白血病,是一种由克隆性增殖的造血干细胞引起的生物学异质性疾病。对新型基因方法认识的增加提高了对AML生物学的理解。最近,代谢组学这一新兴领域表明,在AML的发病机制、进展和治疗过程中,代谢谱存在定性和定量的改变。多种代谢和分子途径调节人体代谢,宿主-微生物组相互作用可能会显著影响这一生物化学机制。已发现微生物群在造血功能、代谢和免疫中发挥重要作用,促成AML的发生。大量研究强调了肠道微生物群(GM)的组成和多样性在AML治疗反应和预后中的重要性。此外,有力证据强调了生态失调与感染性并发症之间的有害联系,而感染性并发症是AML患者发病和死亡的主要原因。到目前为止,几种与微生物群相关的机制已与宿主生理学的特定变化相关联,微生物衍生的代谢产物是其中最重要的一种。它们在体内循环,在局部和全身调节人体状况。细菌代谢功能的广泛多样在包括白血病发生在内的众多过程中起着关键作用。微生物组和代谢组数据的综合分析是更好地理解微生物群、生化改变与AML发病机制之间复杂关系,从而有效预防、治疗和减轻其后果的一个有前景的途径。本综述集中探讨微生物衍生代谢产物在AML中的病理作用和治疗意义。

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