Figure 7.

Model of multiple myeloma development and relapse. We postulate a model combining the recently introduced “Big Bang model”³⁴ and Darwinian type of evolution. According to this model, “Big Bang” dynamics lead to the early establishment of intra-tumor heterogeneity, followed by a Darwinian type of evolution in which different subclones acquire additional aberrations and compete with each other and normal hematopoiesis for access to an appropriate bone marrow niche. Treatment can be thought of as generating a significant population bottleneck, which eradicates some subclones but may simultaneously select for clones with strong driver events that increase proliferation and resistance to apoptosis.