Heterogeneity and Plasticity of Multiple Myeloma
| Authors | |
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| Year of publication | 2013 |
| Type | Chapter of a book |
| MU Faculty or unit | |
| Citation | |
| Description | Modern molecular and cytogenetic approaches have furthered progress in our understanding of MM biology and have led to the development of targeted therapy that has improved management of this incurable disease. Novel agents such as bortezomib, lenalidomide or thalidomide, have increased median survival rates and improved prospects for MM patients resistant to conventional therapy [1, 2]. Despite these therapeutic advances, MM remains a very difficult disease to treat still accompanied by the threat of repeated relapses with a fatal ending. These observations indicate that at least some of the MM cells are not targeted efficiently by current drug therapies. The existence of such persistent populations, called myeloma stem cells (MSC) or myeloma-initiating cells (MIC) has been suspected for more than two decades. However, the cells of origin remain elusive [3-9]. Timeline of growing knowledge about putative MSC is displayed in Figure 1. Discrepancies among myeloma stem cell concepts have arisen in parallel with the high phenotypic heterogeneity of clonal PCs that might be another factor contributing to the failure of therapies and identification of the population responsible for relapse. Myeloma PCs strongly depends on the supportive role of the bone marrow (BM) microenvironment (MEV) – it is a source of essential growth factors, supports survival and dissemination of pathological PCs [10-14]. Furthermore, hypoxic conditions of tumor microenvironments support tumor progression by inducing angiogenesis, maintaining the malignant phenotype and stimulating osteoclastogenesis [15-18]. There is growing evidence that signals from pathological microenvironments can (reversibly) alter the phenotype of PCs. Such plasticity of PCs might result in obvious heterogeneity of MM and generate inconsistencies among myeloma stem cell concepts. |
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