Multiple myeloma (MM) is a cancer that develops from plasma cells, a type of white blood cell normally found in the bone marrow. Healthy plasma cells produce antibodies, which are protein molecules that identify and neutralize foreign invaders like bacteria and viruses. In MM, a single plasma cell becomes cancerous and multiplies uncontrollably within the bone marrow. This accumulation of malignant cells disrupts the normal production of healthy blood cells and immune proteins. The disease is characterized by the excessive production of a single, defective version of the normal antibody protein.
The Foundation: Normal Immunoglobulin Function
Immunoglobulins, also known as antibodies, are Y-shaped proteins that patrol the body to protect against infection. They are composed of four protein chains: two identical heavy chains and two identical light chains, all linked together. The tips of the “Y” shape are the antigen-binding sites, where the antibody recognizes and attaches to a specific foreign substance.
The type of heavy chain determines the class of the immunoglobulin, which dictates its general function and location in the body. There are five main classes, referred to by the letters G, A, M, D, and E, resulting in IgG, IgA, IgM, IgD, and IgE antibodies. For instance, IgG is the most common class in the bloodstream and tissues, while IgA is primarily found in mucosal secretions like tears and saliva. The two types of light chains, kappa (\(\kappa\)) and lambda (\(\lambda\)), are shared across all five heavy chain classes.
The Defining Feature: Understanding the M-Protein
The defining characteristic of multiple myeloma is the presence of an abnormal protein known as the M-protein, or monoclonal protein. This dysfunctional protein is a single, identical type of immunoglobulin or a fragment of one, produced in vast excess by the cancerous plasma cell clone. The M stands for “monoclonal,” meaning all the proteins originate from a single, identical ancestral plasma cell line. Unlike normal, healthy antibodies, which are diverse and target various threats, the M-protein is uniform and ineffective at fighting infection.
This excessive, non-functional protein can accumulate in the blood, causing it to become overly thick, a condition called hyperviscosity. Furthermore, the M-protein, particularly its light chain component, can deposit in and damage organs, most notably the kidneys. The presence of this M-protein in the blood or urine is the most significant laboratory marker of multiple myeloma.
Classifying Multiple Myeloma by Protein Type
Multiple myeloma is classified based on the specific type of M-protein the malignant plasma cells produce. This classification influences the disease’s behavior and potential complications. IgG myeloma is the most frequently encountered type, accounting for approximately 55% to 65% of all cases. The second most common is IgA myeloma, which is found in about 20% of patients.
A distinct and common subtype is Light Chain Myeloma, which occurs in about 15% to 20% of patients. In this form, the cancerous cells only produce large amounts of the light chain component, either kappa or lambda, without the corresponding heavy chain. These isolated light chains are small enough to be filtered out by the kidneys and are detected in the urine, where they are historically called Bence Jones proteins. Rarer types include IgD, IgE, and IgM myelomas, with IgE myeloma representing less than 1% of cases.
Measuring and Monitoring the M-Protein
The M-protein is the primary target for diagnostic testing and monitoring throughout the course of the disease. One standard method is Serum Protein Electrophoresis (SPEP), which separates blood proteins based on their size and electrical charge. The M-protein often appears as a sharp, distinct band, called the “M-spike,” on the SPEP result, allowing for quantification. For patients with Light Chain Myeloma, Urine Protein Electrophoresis (UPEP) is used to detect and measure the Bence Jones proteins excreted in the urine.
A highly sensitive blood test is the Serum Free Light Chain (FLC) assay, which specifically measures the levels of unbound kappa and lambda light chains. This test is particularly useful for light chain myelomas or for detecting disease in patients who produce little or no intact M-protein. The FLC assay is used to calculate the kappa-to-lambda ratio, which is a significant indicator of abnormality if it falls outside the normal range. Tracking M-protein levels, whether intact or as free light chains, helps doctors assess treatment response and signal potential relapse.