Journal
LEUKEMIA & LYMPHOMA
Volume 52, Issue 6, Pages 1066-1079Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2011.562570
Keywords
Mantle cell lymphoma; chemotherapy resistance; cancer stem cells; cancer-initiating cells; non-Hodgkin lymphoma
Categories
Funding
- CONCERN foundation
- [NCI/NIH - CA16672]
- [R21CA141275]
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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.
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