n -乙基-n -亚硝基脲(ENU)改变骨髓中细胞因子的表达,改变骨髓微环境导致白血病的发生。

IF 3.5 4区 医学 Q2 ONCOLOGY
Priyatosh Nath, Chaitali Sarkar, Prosun Tribedi, Debasish Maiti
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引用次数: 0

摘要

骨髓(BM)微环境中的细胞因子在调节造血中起着关键作用。在包括白血病在内的血液系统疾病中,BM细胞因子水平的改变突出了其在白血病发生中的信号作用。因此,阐明脑脊髓瘤中细胞因子表达和信号传导的动力学对于发现新的治疗靶点和改善治疗结果至关重要。本研究假设基底细胞内细胞因子表达的慢性变化驱动白血病的发展。为了验证这一假设,我们设计了一项纵向动物实验,将小鼠注射致癌物n -乙基-n -亚硝基脲(ENU),然后在ENU暴露后的10个不同且均匀的时间点(2-20周)处死。对比分析enu注射小鼠和正常小鼠的BM样本,发现细胞因子表达、氧化应激以及参与DNA合成和细胞周期调节的关键蛋白发生了显著变化。细胞因子、氧化应激平衡及PCNA、NF-κB等蛋白表达的动态变化提示骨髓微环境的调节。这些随暴露时间变化的变化可能会影响造血干细胞(hsc)的细胞过程,从而导致白血病。本研究研究了造血和炎症基因的动态表达,提示细胞因子表达失调在白血病诱导中的关键作用。这项研究的结果将为未来的研究提供信息,旨在阐明细胞因子在白血病发生中的相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
N-ethyl-N-nitrosourea (ENU) alters cytokine expression in the bone marrow modifying the marrow microenvironment to develop leukemia.

Cytokines in the bone marrow (BM) microenvironment play a pivotal role in regulating hematopoiesis. In hematological disease including leukemia, altered levels of BM cytokines highlight the significance of its signaling in leukemogenesis. Elucidating the dynamics of cytokine expression and signaling in the BM is thus essential for uncovering new therapeutic targets and improving treatment outcomes. This study hypothesizes that chronic changes in cytokine expression within the BM drive the development of leukemia. To test this hypothesis, we designed a longitudinal animal experiment wherein mice were injected with the carcinogen N-ethyl-N-nitrosourea (ENU) and subsequently sacrificed at 10 distinct and even time points spanning 2-20 weeks after ENU exposure. Comparative analysis of BM samples from ENU-injected and normal mice revealed significant alterations in cytokine expression, oxidative stress, and key proteins involved in DNA synthesis and cell cycle regulation. The dynamic changes in the expression of studied cytokines, oxidative stress balance, and proteins like PCNA and NF-κB indicate modulation of the marrow microenvironment. These changes, which vary with exposure time, might impact the cellular processes in hematopoietic stem cells (HSCs) to give rise to leukemia. This study investigated the dynamic expression of hematopoietic and inflammatory genes, hinting at the critical role of deregulated cytokine expression in leukemia induction. The outcomes of this study will inform future research aimed at elucidating cytokine interactions in leukemogenesis.

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来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
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