Isolation of spleen lymph during leukemia development

Here we asked whether infiltration of leukemic blasts initiated a response that could be detected in the interstitial fluid phase of the spleen in a rat model known to mimic human acute myeloid leukemia (AML). By cannulating efferent lymphatic vessels, we were able to monitor the response of the spleen microenvironment during leukemia development. Flow cytometric analysis of lymphocytes isolated from spleen lymph showed increased STAT3 and CREB signaling, and proteins related to these pathways were identified with a different profile in leukemic when compared with control spleen lymph. Additionally, SPARC-like 1 protein, recently identified as a promoter of AML cell growth and a biomarker of patient outcome, was locally produced in the spleen and upregulated in the leukemic setting. Thus, interstitial fluid, and its surrogate efferent lymph, can be used to provide unique information about spleen responses and substances released to the general circulation during leukemia development.

本研究旨在探究在模拟人类急性髓系白血病（AML）的大鼠模型中，白血病母细胞浸润是否会触发可在脾脏间质液中检测到的应答反应。通过对输出淋巴管实施插管操作，我们能够在白血病发生进程中实时监测脾脏微环境的应答变化。对从脾淋巴中分离得到的淋巴细胞开展流式细胞术分析后发现，STAT3与CREB信号通路活性显著上调；与对照组脾淋巴相比，白血病模型组脾淋巴中与这两条通路相关的蛋白质呈现出差异化表达谱。此外，SPARC样蛋白1（SPARC-like 1）近期被证实可促进AML细胞增殖并作为患者预后生物标志物，该蛋白可在脾脏局部合成，且在白血病模型中表达上调。综上，脾脏间质液及其替代检测标志物输出淋巴，可用于获取白血病发生过程中脾脏应答反应以及释放入全身循环的物质的独特信息。