Schema illustrating the evolutional clonal architecture in multiple myeloma (MM) at diagnosis and relapse. Noted at diagnosis the clonal diversity with coexistence of dominant and minor subclones that have evolved from a common ancestral tumor-initiating cell or stem cell. The clonal disease at relapse may follow 1 of 3 evolutionary patterns with clones identical to the diagnostic sample and no newly acquired genomic alterations (A), or evolve from the diagnostic clone with linearly derived mutations (B), or, and as seen more commonly in cytogenetically high-risk disease, evolve from an ancestral minor clone(s) with newly acquired genomic mutations or structural rearrangements.