<unk>  is caused by the development of an excessively high number of genetic abnormalities in<unk>  cells or, more particularly, their precursor B cells and<unk> blasts (see<unk>  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<unk>  cell proliferation, survival, apoptosis, adhesion to bone marrow, genome stability, and secretion of monoclonal immunoglobulins. Secondary<unk>  (sPCL) results from the comparatively slow development of<unk>  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<unk>  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 abnormalities 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<unk> s being more closely related to multiple myeloma. Examination of<unk>  cell immunophenotype by measuring certain of their cell surface antigens, particularly Cluster of differentiation. CD markers on<unk>  cells from patients with pPCL differ from those taken form multiple myeloma or sPCL patients. For example: pPCL<unk>  cells more often express CD20 antigen, which is considered important in anchoring<unk>  cells to the bone marrow stroma, than do those on<unk>  cells taken from myeloma patients (50% vs. 17%); pPCL<unk>  cells often lack CD56 antigen which is present on the majority of<unk>  cells taken form multiple myeloma patients; and pPCL<unk>  cells more frequently express CD28 than do sPCL<unk>  cells. Thus, immunophenotyping supports that notion that multiple myeloma, sPCL, and pPCL show critically important fundamental differences that may explain their different clinical presentations, courses, responses to therapy, and prognoses.
Plasma cell leukemia
Waldenström macroglobulinemia
Multiple myeloma
Diffuse large B-cell lymphoma
Macroglobulinemia
Plasmablastic lymphoma
Monoclonal gammopathy of undetermined significance
Primary myelofibrosis