A model of progressive genetic events in t(4;14) MM.

A plasma cell (PC) is immortalized by a t(4;14) translocation, resulting in dysregulated expression of FGFR3 and MMSET in MGUS. Activating mutations occur in either FGFR3 or Ras and are associated with malignant progression of the myeloma clone. Subsequent genetic events, such as c-myc dysregulation by 8q24 translocation,17 lead to extramedullary growth of the tumor cells, resulting in secondary plasma cell leukemia (PCL).