A novel method to investigate drug resistance in the chronic lymphocytic leukemia (CLL) microenvironment: Analysis of CLL Cellular Environment and Response (ACCER)

Abstract

Microenvironments such as lymph nodes allow chronic lymphocytic leukemia (CLL) cells to survive and become drug resistant. There are limited methods to study the to study the contribution of the stromal microenvironment. We have adapted a solid tumor microenvironment cell culture system that provides elements of the CLL microenvironment called Analysis of CLL Cellular Environment and Response (ACCER). We optimized the cell number for patient’s primary CLL cells and HS-5 human bone marrow stromal cell line that will give sufficient cell number and viability with the ACCER. We then determined the amount of collagen type 1 to give the best extracellular matrix to seed CLL cells to the membrane. Finally, we determined that ACCER provide CLL cell protection against cell death following treatment with fludarabine and ibrutinib compared to co-culture conditions. This describes novel microenvironment model to investigate factors that promote drug resistance in CLL.

Keywords:

• Chemotherapeutic approaches
• drug resistance
• lymphoid leukemia

Acknowledgments

We would like to thank the lab of Dr. Alison McGuigan at the University of Toronto for their help in adopting this model for CLL and providing materials for this study. The authors would like to thank Dr. Rebecca Dielschneider and Sara Kost for helpful discussions throughout this study. We would also like to thank the CLL patients of CancerCare Manitoba who have donated their blood for this research. This research was also funded by Research Manitoba.

Disclosure statement

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

Additional information

Funding

This study was supported by the Manitoba Tumour Bank, Winnipeg, Manitoba, funded in part by the CancerCare Manitoba Foundation and the Canadian Institutes of Health Research and is a member of the Canadian Tissue Repository Network.