Therapy induced clonal dynamics in a murine model of MM. (A) Three independent Vk*MYC mice with biclonal or triclonal MM were treated biweekly with escalating doses of bortezomib (0.16-1 mg/kg). SPEP performed at the indicated weeks shows clonal modulation, with arrowheads pointing to the M-spikes secreted by the competed out clones, and arrows indicating the dominant bortezomib-resistant clones. (B) SPEP performed before and after carfilzomib or pomalidomide treatment of Vk*MYC mice with oligoclonal myeloma identifies responsive (arrowheads) and refractory (arrows) clones.