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脾脏微环境在 Eµ-TCL1 转基因小鼠慢性淋巴细胞白血病发展中的作用。

Role of the splenic microenvironment in chronic lymphocytic leukemia development in Eµ-TCL1 transgenic mice.

机构信息

Department of Microbiology, Immunology and Molecular Genetics and Markey Cancer Center, University of Kentucky, Lexington, KY, USA.

Department of Radiation Medicine and Markey Cancer Center, University of Kentucky, Lexington, KY, USA.

出版信息

Leuk Lymphoma. 2022 Aug;63(8):1810-1822. doi: 10.1080/10428194.2022.2045596. Epub 2022 Mar 8.

DOI:10.1080/10428194.2022.2045596
PMID:35258388
Abstract

The chronic lymphocytic leukemia (CLL) microenvironment has been receiving an increasing amount of attention, but there is currently limited data surrounding how the microenvironment affects initial development of CLL. We determined that the spleen is the initial site of CLL growth through monitoring of transgenic Eμ-TCL1 mice that develop CLL. Subsequently, we isolated stromal cells from the spleens of Eμ-TCL1 mice (EMST cells) that induce CLL cell division . Both cell-cell contact and soluble factors were involved in EMST-induced CLL cell division. These stromal cells are present in significantly larger numbers in the spleen than other lymphoid organs. We also noted that splenectomy delayed CLL development in Eμ-TCL1 mice and completely prevented CLL development in adoptive transfer mice. Our findings will allow future studies surrounding the CLL microenvironment to focus upon the splenic stromal cells.

摘要

慢性淋巴细胞白血病(CLL)的微环境越来越受到关注,但目前关于微环境如何影响 CLL 的初始发展的数据有限。我们通过监测患有 CLL 的转基因 Eμ-TCL1 小鼠,确定脾脏是 CLL 生长的初始部位。随后,我们从 Eμ-TCL1 小鼠的脾脏中分离出诱导 CLL 细胞分裂的基质细胞(EMST 细胞)。细胞-细胞接触和可溶性因子都参与了 EMST 诱导的 CLL 细胞分裂。这些基质细胞在脾脏中的数量明显多于其他淋巴器官。我们还注意到,脾切除术可延迟 Eμ-TCL1 小鼠中的 CLL 发展,并可完全阻止过继转移小鼠中的 CLL 发展。我们的发现将使未来围绕 CLL 微环境的研究集中在脾脏基质细胞上。

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