Abstract
Abstract Hematological malignancies harbor sub-populations of cancer-initiating cells (C-ICs) that play important roles in contributing to tumor initiation, progression and drug-resistance. Mantle cell lymphoma (MCL) is highly refractory to conventional chemotherapy regimens as well as new antibody-based therapeutic interventions. We recently observed clonogenic cancer-initiating cells in human MCL (MCL-ICs) and showed that MCL initiating activities were enriched in the cells that lack the prototypic B cell marker CD19. We discovered that MCL-ICs are highly tumorigenic and display self-renewal capacities in vivo; in contrast, CD45+CD19+ MCL cells, which constitute the vast majority of cells within the tumors, show no self-renewal capacities and greatly reduced tumorigenicity. Given the newly appreciated roles of cancer-initiating cells in the drug resistance of cancers, it is critical to investigate whether MCL-ICs play roles in drug resistance of human MCL. We have discovered MCL-ICs were more resistant to several clinically-relevant chemotherapeutic agents in combination or in a single regimen compared to CD45+CD19+ cells. The drug resistance of MCL-ICs was largely due to quiescent properties with enriched ABC transporters. In conclusion, designing novel therapies to kill MCL-ICs may prevent relapse and increase patient survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3400. doi:10.1158/1538-7445.AM2011-3400
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