Pathway to multiple myeloma. The transition of MGUS to plasma cell leukemia has been traditionally represented as a linear pathway (A). However, it is more likely that the pathway to myeloma is through branching pathways typical of those that are associated with the evolution of species (B). The key molecular events leading to disease evolution are represented as diamonds and indicate distinct patterns of driver mutations. This simple branching model clearly has implications for targeted treatment because the multiple distinct subclones could lead to differential responses to treatment. Reprinted with permission from Morgan et al.²³