Multiple myeloma is a multifocal plasma cell neoplasm that affects the bone marrow and is associated with the production of a serum and urinary monoclonal protein. The cause is a progressive unregulated proliferation of plasma cells that accumulate in the bone marrow. These cells secrete immunoglobulin (Ig) in excess, usually: 57% IgG, 21% IgA, 1% IgD, IgM, IgE, only rarely in 18% of cases of light chains alone. The proliferation of multiple myeloma interferes with the normal production of cells in the bone marrow and usually results in anemia. In some cases, leukopenia and thrombocytopenia are also observed. Another feature is that multiple myeloma cells secrete certain substances that stimulate the osteoclasts and inhibit the osteoblasts, which results in an exaggerated destruction of the bone tissue with the subsequent pathological fracture, in many cases hypercalcemia.

Although the first case of multiple myeloma was diagnosed in 1845, this disease was considered a bone tumor for a long time. This fact made epidemiological investigations difficult and only in the last decades was it considered as a monoclonal gammopathy. In the first patients studied, the presence of a special protein called Bence-Jones protein was detected in the urine.

What is the pathogenesis of Multiple Myeloma?

The pathogenesis includes monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic MM has been determined that translocations that involve the locus of the immunoglobulin heavy chain on chromosome 14q32, initiate and maintain the proliferative clone, which is accompanied by Other chromosomal alterations and dysregulation of genes, especially cyclins D1, D2 or D3, constitute a prognostic classification, where the genetic profile plays an important role.

What is the M protein?

As mentioned earlier, a characteristic feature of multiple myeloma is the production of a monoclonal protein (M-protein). The test used to measure the amount of monoclonal protein in the blood or urine is protein electrophoresis.

This M-protein is synthesized by malignant plasma cells are immunoglobulin molecules or parts of them. The amount of protein produced and secreted into the serum and urine reflects the state of the myeloma present in the body at any given time.

What is Serum Protein Electrophoresis?

Protein electrophoresis is a laboratory test based on the separation of proteins by applying an electric field. When a sample with a mixture of different proteins is subjected to electrophoresis, the different proteins in the mixture will separate according to their electrical charge.

The serum contains a variety of different proteins that will be separated by electrophoresis in five or six fractions (according to the method used by the laboratory). These fractions (also known as “zones” or “regions”) are called Albumin, Alpha 1, Alpha 2, Beta (which can be separated into Beta 1 and Beta 2), and Gamma. Polyclonal (normal) immunoglobulins are found in the gamma zone.

The normal immunoglobulins present in the serum are diverse and present slight differences in their structure and electrical charge. For that reason, when subjected to electrophoresis, they form a large area, which is diffuse and symmetric, without any visible deformation.

The monoclonal proteins are produced by a clone of plasma cells, so all the molecules are identical and have the same electrical charge. That is the reason why in the electrophoresis a monoclonal protein will migrate as a narrow peak (this peak almost always appears in the gamma zone, but sometimes it can be present in Beta 2 or Beta 1, or even in the Alpha 2 zone, although the latter is rare). Serum electrophoresis can be used to search for a monoclonal protein, as well as to monitor the amount of monoclonal protein present.

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