About Multiple Myeloma.

Multiple myeloma is characterized by malignant plasma cells that reproduce uncontrollably.

Plasma cells are a type of white blood cell that produces and secretes antigen-specific antibodies. (Antigens are substances that are foreign to the body; antibodies are produced naturally by the body to fight off antigens that can cause infection and disease). The malignant plasma cells of multiple myeloma are derived from B-cells (a type of white blood cell produced in the lymphatic tissues and bone marrow) after a number of differentiation and proliferation processes.

Multiple myeloma plasma cells tend to localize within the bone marrow, although they may be found in other parts of the body as well.

Multiple myeloma cells are monoclonal, that is, they are derived from a single B-cell that has undergone cytogenetic changes (genetic changes at the cellular level). Multiple myeloma patients are frequently found to have an abnormal karyotype, or cytogenetic indicator. Abnormalities are commonly found on chromosome 13 and chromosome 11, although others may also be involved. Cytogenetic profiles of a patient's chromosomes can be used as a guide for predicting disease progression.

The bone marrow environment is an organized meshwork of cells that are collectively called stromal cells. Multiple myeloma cells adhere to the stromal cells in the bone marrow; there they inhibit osteoblastic (new bone cell growth) activity. Adhesion of the multiple myeloma cell stimulates production of interleukin-6, a growth factor required for survival of the multiple myeloma cells. Interleukin-6 stimulates increased osteoclastic activity (movement of calcium out of bones and into the bloodstream). It is the increased osteclastic activity (process of bone cells leaving bone and being drawn into the blood) stimulated by interleuken-6, plus inhibited growth of new bone cells which result in bone lesions (lytic lesions), osteoporosis, and hypercalcemia (too much calcium in the bloodstream).

Multiple myeloma cells produce excessive monoclonal proteins (all the same type of proteins), which are classified as heavy amino acid chains and light amino acid chains. The terms heavy and light refer to the molecular weight of the protein. The monoclonal proteins, also known as M proteins, antibodies, or immunoglobulins, are recognized as IgA, IgD, IgG, IgE or IgM. These M proteins can be detected via protein electophoresis, a process that uses an electrical current to separate the various proteins in a sample of blood. The M protein level is referred to as the M-spike. In multiple myeloma patients the M protein is most commonly IgG or IgA.

The light amino acid chains are of two types: kappa and lambda. Kappa is twice as prevalent as lambda. When detected in the urine the light chain fragments are called Bence-Jones proteins. They are followed as an indicator of disease activity and progression.