4.3 Article

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

Journal

LEUKEMIA & LYMPHOMA
Volume 63, Issue 8, Pages 1810-1822

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2022.2045596

Keywords

Cell lines and animal models; lymphoid leukemia; cytokine production and paraneoplastic conditions; basic biology; lymphocytes

Funding

  1. National Institutes of Health, National Cancer Institute [CA 165469]
  2. National Center for Advancing Translational Sciences [UL1TR001998, UL1TR000117]
  3. Markey Cancer Center, University of Kentucky
  4. National Institutes of Health, National Cancer Institute T32 grant [CA165990]
  5. Biospecimen Procurement and Translational Pathology shared resource facilities of the University of Kentucky Markey Cancer Center [P30 CA177558]
  6. Office of the Vice President for Research
  7. Markey Cancer Center
  8. National Cancer Institute Center Core [P30 CA177558]

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The study revealed that the spleen is the initial site of chronic lymphocytic leukemia (CLL) growth, with splenic stromal cells playing a crucial role in inducing CLL cell division. Splenectomy was found to delay CLL development, suggesting the importance of splenic stromal cells in CLL progression.
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 E mu-TCL1 mice that develop CLL. Subsequently, we isolated stromal cells from the spleens of E mu-TCL1 mice (EMST cells) that induce CLL cell division in vitro. 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 E mu-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.

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