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

James P. Collard; Mary K. McKenna; Sunil K. Noothi; Sara S. Alhakeem; Jacqueline R. Rivas; Vivek M. Rangnekar; Natarajan Muthusamy; Subbarao Bondada

doi:10.1080/10428194.2022.2045596

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

James P. Collard, Mary K. McKenna, Sunil K. Noothi, Sara S. Alhakeem, Jacqueline R. Rivas, Vivek M. Rangnekar, Natarajan Muthusamy, Subbarao Bondada

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1810-1822
Number of pages	13
Journal	Leukemia and Lymphoma
Volume	63
Issue number	8
DOIs	https://doi.org/10.1080/10428194.2022.2045596
State	Published - 2022

Bibliographical note

Funding Information:
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. 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.

Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

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

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/10428194.2022.2045596

Cite this

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title = "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, basic biology, cytokine production and paraneoplastic conditions, lymphocytes, lymphoid leukemia",

author = "Collard, {James P.} and McKenna, {Mary K.} and Noothi, {Sunil K.} and Alhakeem, {Sara S.} and Rivas, {Jacqueline R.} and Rangnekar, {Vivek M.} and Natarajan Muthusamy and Subbarao Bondada",

note = "Funding Information: 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. 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. Publisher Copyright: {\textcopyright} 2022 Informa UK Limited, trading as Taylor & Francis Group.",

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AU - McKenna, Mary K.

AU - Noothi, Sunil K.

AU - Alhakeem, Sara S.

AU - Rivas, Jacqueline R.

AU - Rangnekar, Vivek M.

AU - Muthusamy, Natarajan

AU - Bondada, Subbarao

N1 - Funding Information: 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. 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. Publisher Copyright: © 2022 Informa UK Limited, trading as Taylor & Francis Group.

PY - 2022

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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