Stem-like tumor cells confer drug resistant properties to mantle cell lymphoma

Abstract

We recently identified clonogenic malignant stem cell populations in human mantle cell lymphoma (MCL), a particularly deadly subtype of non-Hodgkin lymphoma (NHL). We discovered that CD45+CD19− MCL cells, which we termed MCL-initiating cells (MCL-ICs), are highly tumorigenic and display self-renewal capacity in vivo; in contrast, CD45+CD19+ MCL cells, which constitute the vast majority of cells within the tumors, show no self-renewal capacity and greatly reduced tumorigenicity. Given the newly appreciated role of cancer-initiating cells in the drug resistance of cancers, it is critical to investigate whether CD45+CD19− MCL-ICs play a role in the drug resistance of human MCL. We discovered that MCL-ICs were more resistant to clinically relevant chemotherapeutic agents, in combination or in a single regimen, compared to CD45+CD19+ cells, and that this drug resistance was largely due to quiescent properties with enriched ABC transporters. In conclusion, designing novel therapies to kill CD45+CD19− MCL-ICs may prevent relapse and increase patient survival.

Keywords:

• Mantle cell lymphoma
• chemotherapy resistance
• cancer stem cells
• cancer-initiating cells
• non-Hodgkin lymphoma

Acknowledgements

The tissue samples were provided by the University of Texas M. D. Anderson Cancer Center Satellite Lymphoma Tissue Bank, which was supported by Institutional Core Grant # NCI/NIH – CA16672. This work is supported by R21CA141275 and the CONCERN foundation.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal .