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  • Myeloma is a malignancy of terminally differentiated B cells (plasma cells) that produces a complete monoclonal immunoglobulin (Ig) protein or a free light chain (FLC).

  • Clinical and laboratory manifestations are heterogeneous but typically include:

    — A monoclonal Ig 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 Ig secretion by residual normal plasma cells, which predisposes to infections.

    — Hypercalcemia as a result of osteolysis.

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

    — Myeloma cell proliferation in marrow leading to impaired hematopoiesis.

    — Osteolytic bone disease.


  • Myeloma accounts for more than 1.8% of all malignancies and 10% of hematologic neoplasms.

  • Most patients are diagnosed between ages 65 and 74 years; only 4% of cases occur before age 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, whether clinically identified or not, by a condition known as essential monoclonal gammopathy (MG), also known as monoclonal gammopathy of unknown significance (MGUS), which may develop years before the diagnosis of myeloma. Among patients with MG, progression to myeloma is approximately 1% per year.

  • Genome-wide association studies identified seven single-nucleotide polymorphisms associated with risk for MG and myeloma, including those at chromosomes 2p23.3, 3p22.1, 3q26.2, 6p21.33, 7p15.3, 17p11.2, and 22q13.1, although 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 69–1.

  • Myeloma cell Ig 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 number changes. Common genomic aberrations are shown in Table 69–1.

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

  • Patients with hyperdiploid myeloma, 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 cells with the marrow microenvironment plays a key role in disease progression and drug resistance.


Myeloma stages, ...

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