Abstract 3045: Defining an elusive multiple myeloma stem cell population in mice

Abstract

Abstract Multiple Myeloma (MM) is a debilitating disease of proliferating and malignant plasma cells that is currently incurable. The ability of monoclonal recurrence of disease suggests it might arise from a stem cell-like population capable of self-renewal. The difficulty to isolate the cancer stem-like cell in MM in both mice and men has introduced confusion toward this hypothesis. XBP1s is a key positive regulator for unfolded protein response and a master transcription factor for plasma cell development. It was previously reported that transgenic overexpression of XBP1s in the B cell lineage of mice (XBP1s-Tg), induces a multiple myeloma phenotype resembling human MM. We have now defined a post-germinal center, pre-plasma B cell population that was significantly increased in XBP1s-Tg mice as the hallmarks of MM was demonstrated. This non-memory B cell population resembled a stem/progenitor cell population, with increased expression of aldehyde dehydrogenase (ALDH), Notch1 and c-kit. Importantly, utilizing an in vitro culture for differentiating plasma cells, the increased population began to differentiate into plasma cells, increasing in size and gaining CD138 expression, the hallmark marker for plasma cells. In conclusion, we have defined a transitional pre-plasma cell population that could potentially be a stem/progenitor population of multiple myeloma. These results provide a novel insight into stem cell biology with regard to multiple myeloma and the use of murine models of myeloma to study the disease. Citation Format: Joshua Kellner, Yunpeng Hua, Bei Liu, Zihai Li. Defining an elusive multiple myeloma stem cell population in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3045. doi:10.1158/1538-7445.AM2014-3045