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

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 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 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.

Keywords:

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

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

A special thanks to the Markey Cancer Center Hematology-Oncology Clinic nurses for help in collecting patient samples. We would also like to thank Dr. Jessica Moorleghan for training lab members in mouse splenic ultrasound and volume analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from the National Institutes of Health, National Cancer Institute (CA 165469) (N.M., V.M.R., and S.B.) CA217934 (SB). This research received support from the National Center for Advancing Translational Sciences (UL1TR001998 and UL1TR000117) and a grant from the Markey Cancer Center, University of Kentucky to SB. M.K.M. and J.R.R. were supported by National Institutes of Health, National Cancer Institute T32 grant CA165990. JRR is a Fellow of the Leukemia and Lymphoma Society. This research was supported by the Biospecimen Procurement and Translational Pathology shared resource facilities of the University of Kentucky Markey Cancer Center (P30 CA177558). The Flow Cytometry & Cell Sorting core facility is supported in part by the Office of the Vice President for Research, the Markey Cancer Center, and a National Cancer Institute Center Core Support Grant (P30 CA177558) to the University of Kentucky Markey Cancer Center.