Secondary PCL (sPCL) is diagnosed in 1-4% of patients known to have had multiple myeloma for a median time of ~21 months. It is the terminal phase of these patients myeloma disease. sPCL patients typically are highly symptomatic due to extensive disease with malignant plasma cell infiltrations in, and failures of, not only the bone marrow but also other organs. They have failed or broke through one or more treatment regimens and therefore may also show some of the toxic effects of these treatments. PCL is caused by the development of an excessively high number of genetic abnormalities in plasma cells or, more particularly, their precursor B cells and plasmablasts (see plasma cells). This genetic instability is due to a myriad of acquired abnormalities including gene mutations; single nucleotide polymorphisms; depletions and duplications of parts of a gene, larger portion of a chromosome, or even an entire arm of a chromosome; translocations, deletions, and duplications of entire chromosomes; and increases and decreases in the expression of intact genes due to, e.g. the methylation of gene promotors and various less direct effects. These genetic abnormalities effect the Wnt signaling pathway, regulation of the cell cycle, RNA metabolism, protein folding, and cadherin-related cell adherence to extracellular matrix. These effects in turn control plasma cell proliferation, survival, apoptosis, adhesion to bone marrow, genome stability, and secretion of monoclonal immunoglobulins. Secondary plasma cell leukemia (sPCL) results from the comparatively slow development of plasma cell/plasma cell precursor genetic abnormalities which initially create a clone of cells that cause the premalignant condition of monoclonal gammopathy of undetermined significance. In a very small percentage of these cases, the progressive development of further genetic abnormalities serially create a clone(s) of plasma cells that cause the more serious but still premalignant disorder of smoldering multiple myeloma, overt myeloma cancer, and ultimately sPCL. In contrast to sPCL, pPCL presents "de novo" with a broad range of genetic abnormalities. For example, advanced methods for examining the genome viz., whole-exome sequencing and gene expression profiling, have identified 166 non-silent gene variants per pPCL patient sample at the time of diagnosis. These abnormalities are similar but not identical to those detected in sPCL while the abnormalies detected in sPCL more closely resemble those detected in multiple myeloma than do those of pPCL: the genetic data support the clinical data in suggesting that sPCL and pPCL are distinct diseases with sPCL among the two PCLs being more closely related to multiple myeloma.