Metabolic reprogramming in the CLL TME; potential for new therapeutic targets

IF 5 3区 医学 Q1 HEMATOLOGY Seminars in hematology Pub Date : 2024-06-01 DOI:10.1053/j.seminhematol.2024.02.001
Helga Simon-Molas , Chiara Montironi , Anna Kabanova , Eric Eldering
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Abstract

Chronic lymphocytic leukemia (CLL) cells circulate between peripheral (PB) blood and lymph node (LN) compartments, and strictly depend on microenvironmental factors for proliferation, survival and drug resistance. All cancer cells display metabolic reprogramming and CLL is no exception – though the inert status of the PB CLL cells has hampered detailed insight into these processes. We summarize previous work on reactive oxygen species (ROS), oxidative stress, and hypoxia, as well as the important roles of Myc, and PI3K/Akt/mTor pathways. In vitro co-culture systems and gene expression analyses have provided a partial picture of CLL LN metabolism. New broad omics techniques allow to obtain molecular and also single-cell level understanding of CLL plasticity and metabolic reprogramming. We summarize recent developments and describe the new concept of glutamine addiction for CLL, which may hold therapeutic promise.

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CLL TME 中的代谢重编程;新治疗靶点的潜力
慢性淋巴细胞白血病(CLL)细胞在外周血(PB)和淋巴结(LN)之间循环,其增殖、存活和耐药性严格依赖于微环境因素。所有癌细胞都会进行代谢重编程,CLL 也不例外--尽管 PB CLL 细胞的惰性状态阻碍了对这些过程的详细了解。我们总结了以前在活性氧(ROS)、氧化应激和缺氧方面的工作,以及 Myc 和 PI3K/Akt/mTor 通路的重要作用。体外共培养系统和基因表达分析提供了 CLL LN 代谢的部分情况。新的全息技术可从分子和单细胞层面了解 CLL 的可塑性和代谢重编程。我们总结了最近的研究进展,并描述了CLL谷氨酰胺成瘾的新概念,这可能具有治疗前景。
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来源期刊
Seminars in hematology
Seminars in hematology 医学-血液学
CiteScore
6.20
自引率
2.80%
发文量
30
审稿时长
35 days
期刊介绍: Seminars in Hematology aims to present subjects of current importance in clinical hematology, including related areas of oncology, hematopathology, and blood banking. The journal''s unique issue structure allows for a multi-faceted overview of a single topic via a curated selection of review articles, while also offering a variety of articles that present dynamic and front-line material immediately influencing the field. Seminars in Hematology is devoted to making the important and current work accessible, comprehensible, and valuable to the practicing physician, young investigator, clinical practitioners, and internists/paediatricians with strong interests in blood diseases. Seminars in Hematology publishes original research, reviews, short communications and mini- reviews.
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