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  • Myeloma is a malignancy of terminally differentiated B cells (plasma cells) that produces a complete and/or partial (light chain) monoclonal immunoglobulin protein.

  • Clinical and laboratory manifestations are heterogeneous, but typically include:

    — A monoclonal immunoglobulin in plasma and/or monoclonal light chains in plasma and urine. In rare cases, the cells do not secrete a monoclonal protein in the plasma.

    — Decreased polyclonal immunoglobulin secretion by residual normal plasma cells, which predispose to infections.

    — Myeloma cell proliferation in marrow leading to impaired hematopoiesis.

    — Osteolytic bone disease.

    — Often hypercalcemia as a result of osteolysis.

    — Sometimes renal dysfunction as a result light chain casts or hypercalcemia.

  • Nearly 85 percent of newly diagnosed myeloma patients who have gene-expression-defined good-risk disease fare so well with therapy that the prospect of cure now appears tenable.


  • Myeloma accounts for more than 1 percent of all malignancies and for 10 percent of hematologic neoplasms.

  • The age-adjusted incidence of myeloma is affected by gender and ethnicity: White men 6.6/100,000 persons, white females 4.2/100,000, black men 13.7/100,000 and black females 9.9/100,000.

    — The incidence of myeloma increases with age exponentially from age 40 years onward. Occasional cases occur in individuals in the third and fourth decade of life.

  • Analysis of the aggregate of studies does not support a role for chemical agents, such as benzene or other solvents, pesticides, herbicides, or others as causative factors.

  • Radiation, once thought to be a cause, appears not to be after reanalysis of the data in the Japanese population surviving the atomic bomb blasts.

  • Several studies indicate an increased risk of myeloma in overweight and obese individuals. This relationship might be mediated by elevated IL-6 secreted by fat cells and fatty tissue stroma.


  • Myeloma may result from errors in the process of immunoglobulin class switching, somatic hypermutation, or antigen receptor gene rearrangement of variable (V), diversity (D) and joining (J) gene segments (VDJ recombination) leading to mutational errors (double-strand DNA breaks) and, for example, translocations involving the IgH gene, fusing it to genes involved in cell proliferation or cell survival, and a resultant neoplastic change in late B-cell progenitor.

  • Among patients with essential monoclonal gammopathy, progression to a progressive B-cell neoplasm (e.g., lymphoma, myeloma, AL amyloidosis) is 1 percent per year.

    — Many patients with myeloma have a preceding period of essential monoclonal gammopathy.

  • Genetic abnormalities by standard cytogenetic and fluorescence in situ hybridization (FISH) are evident in two-thirds of patients with myeloma.

  • DNA hyperdiploidy is present in about three-quarters of all patients.

  • Typically, there are multiple abnormalities in each karyotype.

  • Hyperdiploid myeloma typically has multiple trisomies of odd numbered chromosomes 3, 5, 7, 9, 11, 15, 19, and 21.

  • Nonhyperdiploid myeloma usually is associated with immunoglobulin heavy chain (IgH) gene translocations located at chromosome 14q32 observed in about two-thirds of patients by FISH and in some patients translocations involving the ...

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