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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

    — Renal dysfunction as a result of light chain casts or hypercalcemia


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

  • Most patients are diagnosed between ages 65 to 74 years of age; only 4% of cases occur before 45 years. The median age of onset is 69 years.

  • Men are affected more frequently than women (1.6:1 ratio). Individuals of African descent have twice the prevalence as those of European descent.

  • Myeloma is always preceded by a condition known as essential monoclonal gammopathy (MG), which may develop years before the diagnosis of myeloma. Among patients with MG, progression to myeloma is 1% per year.

  • Genome-wide association studies identified six single nucleotide polymorphisms (SNPs) associated with risk for MG and myeloma, including 2p23.3, 3p22.1, 3q26.2, 6p21.33, 7p15.3, 17p11.2, and 22q13.1. The identified genes (DNMT3A, ULK4, TERC, PSORS1C1, CDCA7L/DNAH1, TNFRSF13B, and CBX7) have not been validated as myeloma-driver genes.


  • Myeloma cells are derived from postgerminal-center marrow plasmablasts/plasma cells. Stages of evolution from MG to plasma cell leukemia are shown in Figure 68–1.

  • Myeloma cell immunoglobulin heavy chain (IgH) variable genes present somatic mutations in the absence of intraclonal variation or ongoing somatic hypermutation.

  • Myeloma is characterized by karyotypic abnormalities including translocations and copy change numbers. Common genomic aberrations are shown in Table 68–1.

  • DNA hyperdiploidy is present in up to 60% of patients.

  • Hyperdiploid myeloma patents, typically IgG kappa-type with bone involvement, show gains of odd-numbered chromosomes, including 15, 9, 5, 19, 3, 11, 7, and 21 (ordered by decreasing frequency).

  • Nonhyperdiploid myeloma usually is associated with IgH gene translocations located at chromosome 14q32 and in some patients with translocations involving the λ light chain locus on chromosome 22. Translocations involving the κ locus on chromosome 2 are rare.

  • Deletions of chromosomes 13 (resulting in RB1 gene and miRNA-15a/16-1 cluster dysregulation) and 17 (involving the TP53 locus), and amplification of chromosome 1q21 have been associated with a poor prognosis.

  • The interaction of myeloma cell with the marrow microenvironment plays a key role in disease progression and drug resistance.


Myeloma stages, from essential monoclonal gammopathy (MG) to plasma cell leukemia. Myeloma evolves from a benign condition called essential monoclonal gammopathy ...

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