There are no known causes of multiple myeloma, except from underlying causes of all cancer disease.
How a plasma cell is transformed into a myeloma cell is not completely understood, but there are many genetic changes present in a myeloma cell. The genetic changes are either chromosomal (translocations and deletions) or mutations in single genes.Most translocations have breakpoints in the gene region of the heavy chain of the immunoglobulin molecule, which indicates that the changes occur when the B lymphocyte is changing the phenotype from IgM to one of the other immunoglobulin types.The mutations are often in genes that encode proteins important for cell growth, cell differentiation and cell death. These mutations do not occur in the germ cells (sperm cells and ova) and myeloma is therefore not inheritable in the usual meaning of the word. However, there are indications of some overrepresentation of myeloma and related diseases in the closest family. This disposition cannot be tested for. It is possible that all factors giving rise to mutations (for example ionizing radiation) may contribute to the development of myeloma. Several mutations are probably a prerequisite for the development of a plasma cell into a myeloma cell.
Multiple myeloma always develops from MGUS (monoclonal gammopathy of undetermined significance). The risk that MGUS progresses into malignant disease is about 1% annually.