Abstract PL3-2: Translating multiple myeloma stem cells

Abstract

Abstract Emerging evidence suggest that many human cancers consist of phenotypically and functionally heterogeneous cell types. Moreover, the capacity for clonogenic growth and self-renewal may be restricted to specific cell populations. In multiple myeloma, malignant plasma cells make up the vast majority of tumor cells and are responsible for symptoms arising within the disease. However, myeloma plasma cells also appear to be terminally differentiated like their normal counterparts and incapable of long-term proliferation. Similar to other laboratories, we have identified minor populations of B cells that share the identical immunoglobulin gene rearrangements as the malignant plasma cells in most myeloma patients. We have further studied the functional capacity of these clonotypic B cells and found that they have ability to produce ectopic tumor growth both in vitro and in immunodeficient mice in which they recapitulate human disease. Moreover, these cells are relatively resistant to several agents currently used to treat multiple myeloma suggesting that they persist following treatment and are responsible for tumor regrowth and disease relapse. In order to inhibit these drug resistant cancer stem cells, we have studied cellular pathways that regulate the self-renewal of normal adult stem cells and found that several, including the developmental pathway Hedgehog, are potential therapeutic targets. Lastly, we have begun to develop biomarker strategies to serially quantify myeloma stem cells in patients undergoing treatment. We hope that these will serve as useful endpoints as myeloma stem cell directed therapies enter the clinic. Citation Information: Clin Cancer Res 2010;16(7 Suppl):PL3-2