Isolation of lymph shows dysregulation of STAT3 and CREB pathways in the spleen and liver during leukemia development in a rat model

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2023-01-26 DOI:10.1111/micc.12800

Eli Sihn Samdal Steinskog, Kenneth Finne, Marianne Enger, Lars Helgeland, Per Ole Iversen, Emmet McCormack, Helge Wiig, Olav Tenstad

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引用次数: 1

Abstract

Background and aims

Acute myeloid leukemia (AML) is a heterogeneous malignant condition characterized by massive infiltration of poorly differentiated white blood cells in the blood stream, bone marrow, and extramedullary sites. During leukemic development, hepatosplenomegaly is expected to occur because large blood volumes are continuously filtered through these organs. We asked whether infiltration of leukemic blasts initiated a response that could be detected in the interstitial fluid phase of the spleen and liver.

Material and Methods

We used a rat model known to mimic human AML in growth characteristics and behavior. By cannulating efferent lymphatic vessels from the spleen and liver, we were able to monitor the response of the microenvironment during AML development.

Results and Discussion

Flow cytometric analysis of lymphocytes showed increased STAT3 and CREB signaling in spleen and depressed signaling in liver, and proteins related to these pathways were identified with a different profile in lymph and plasma in AML compared with control. Additionally, several proteins were differently regulated in the microenvironment of spleen and liver in AML when compared with control.

Conclusion

Interstitial fluid, and its surrogate efferent lymph, can be used to provide unique information about responses in AML-infiltered organs and substances released to the general circulation during leukemia development.

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在大鼠白血病模型中，淋巴分离显示脾脏和肝脏中STAT3和CREB通路的失调

背景和目的急性髓性白血病(AML)是一种异质性恶性疾病，其特征是血流、骨髓和髓外部位大量低分化白细胞浸润。在白血病的发展过程中，由于大量的血液不断地通过这些器官过滤，预计会发生肝脾肿大。我们询问白血病细胞的浸润是否引发了一种反应，这种反应可以在脾和肝的间质液相中检测到。材料和方法我们使用了一种已知在生长特征和行为上模仿人类AML的大鼠模型。通过在脾和肝的传出淋巴管中插管，我们能够监测AML发展过程中微环境的反应。淋巴细胞流式细胞分析显示，脾脏STAT3和CREB信号通路增加，肝脏信号通路抑制，与对照组相比，AML患者淋巴和血浆中与这些通路相关的蛋白具有不同的特征。此外，与对照组相比，AML中脾脏和肝脏微环境中的几种蛋白质受到不同的调节。结论间质液及其替代物传出淋巴可为白血病发生过程中aml浸润器官的反应和释放到循环中的物质提供独特的信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.

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