The Search for Multiple Myeloma Stem Cells: The Long and Winding Road Grzegorz Wladyslaw Basak, Ewa Carrier  Biology of Blood and Marrow Transplantation  Volume 16, Issue 5, Pages 587-594 (May 2010) DOI: 10.1016/j.bbmt.2009.10.024 Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 The proposed model of myelomagenesis. Healthy B lymphocytes that undergo a first mutation give rise to the clones of premalignant B lymphocytes expressing identical immunoglobulin genes (ie, clonotypic B cells). Mutations accumulate in MGUS B cells until the key mutation transforms premalignant B lymphocytes into malignant MM B lymphocytes. These malignant MM B lymphocytes undergo isotype switching and may gain/retain the self-renewal capacity characteristic of stem cell fraction. Presumably, their population could expand because of symmetric cell divisions, whereas a proportion of resulting MM B lymphocytes differentiates to MM plasma cells (possibly because of leaving the MM stem cell niche). It is also possible that MM stem cells differentiate to mature MM plasma cells and MM stem cells at the same time (a process known as asymmetric cell division). MM plasma cells retain their self-renewal capacity to a limited extent; however, in certain situations, the MM plasma cells can redifferentiate and acquire properties of MM stem cells. Biology of Blood and Marrow Transplantation 2010 16, 587-594DOI: (10.1016/j.bbmt.2009.10.024) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions