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The Role of M Protein in Myeloma

Medically reviewed by Mark Levin, M.D.
Written by Maureen McNulty
Posted on June 16, 2021

M protein is a molecule that is not normally made by the body. The “M” technically stands for “monoclonal,” but M protein is often referred to as myeloma protein. High amounts of M protein in a person’s blood or urine may be a sign they have multiple myeloma — but the presence of M proteins could also indicate other types of plasma cell tumors.

What Is M Protein?

M protein is made by abnormal plasma cells. In order to understand M protein, it helps to know more about how plasma cells work.

Plasma cells are part of the immune system. They develop from B cells (a type of white blood cell). A plasma cell’s job is to make proteins that fight off germs like bacteria and viruses. These proteins are called antibodies or immunoglobulins. Plasma cells produce antibodies using genes that tell the cell how to make the antibody protein. As plasma cells develop, each cell’s antibody-producing genes become rearranged in a unique way. This means that each plasma cell is genetically different and makes a slightly different antibody. Having a wide variety of antibodies helps in locking in on different targets and fighting off different types of infections.

Abnormal or cancerous plasma cells don’t develop in the usual way. They arise when one single plasma cell becomes damaged and produces many clones of itself. These cloned cells all have the same gene rearrangements and make monoclonal immunoglobulins (antibodies that are exactly the same). This type of protein goes by many names, including M protein, myeloma protein, monoclonal protein, M spike, or paraprotein.

M proteins do not work properly. They can’t fight germs as well as other antibodies. They can also damage the kidneys.

What Do High Levels of M Protein Mean?

High M-protein levels are a sign that a person has abnormal plasma cells. M protein can be a sign of several different types of diseases. Tests that measure M protein may be used to:

  • Diagnose a condition
  • Determine the stage of a disease
  • Find out whether the condition is getting worse
  • Determine how well treatments are working

Diagnosing Multiple Myeloma

Having M protein in your system may be a sign of multiple myeloma. Most people with myeloma have M protein in their blood or urine. If a doctor finds you have M protein, they will likely recommend other tests before making a diagnosis of multiple myeloma. These diagnostic tests may include:

  • Imaging tests
  • Genetic tests
  • Bone marrow biopsies (taking a sample of the soft tissue found inside the bones)
  • Other blood tests

Diagnosing Other Diseases Using M Protein

Finding M protein in the blood or urine does not necessarily mean a person has multiple myeloma. There are several other plasma cell disorders that may also result in high levels of M protein.

Lower levels of M protein may mean a person has monoclonal gammopathy of undetermined significance (MGUS). This condition occurs when there are small numbers of abnormal plasma cells in the bone marrow. People with MGUS don’t have any signs or symptoms of multiple myeloma, but they have an increased risk of developing this blood cancer. Each year, there is a 1 percent chance that a person’s MGUS will turn into myeloma. MGUS can also sometimes lead to other diseases such as lymphoma, Waldenström macroglobulinemia, or amyloidosis. MGUS can be seen as the first step toward myeloma, followed by smoldering multiple myeloma (SMM).

People with SMM — also called asymptomatic myeloma — have increased levels of plasma cells but lack any other myeloma symptoms. However, smoldering myeloma usually turns into multiple myeloma eventually. In recent years, a consensus has developed that treating SMM is beneficial but can be delayed in some circumstances.

If an M-protein test reveals that you have a condition like SMM or MGUS, you can take steps to protect your health. Knowing you are at risk for developing a condition like myeloma can help you catch it early. People with SMM or MGUS should have regular follow-up visits and tests. If the condition transforms into myeloma, it can be found and treated right away, which may lead to a better outcome.

M Protein in Monitoring Diseases and Treatments

After a condition is diagnosed, doctors may rely on M-protein levels to provide other information. M-protein levels can help in determining myeloma stages (how advanced the condition is). Doctors commonly use two systems to classify myeloma into stages. One of them, the Durie-Salmon Staging System, bases stages in part on how high M-protein levels are.

Doctors may also continue measuring M-protein levels after diagnosis to gauge when a disease is getting worse. For example, M-protein levels may indicate when SMM or MGUS has transformed into myeloma. They can also help show whether myeloma is becoming more advanced, which may indicate that a person’s treatment plan should change.

M-protein levels can also show whether myeloma treatments are working. If a treatment is successful, M-protein levels will decrease and eventually reach zero.

How Is M Protein Measured?

Some tests measure M-protein levels while others analyze the M-protein type. It is important to know which type of M protein your plasma cells are producing. Antibodies, including M proteins, are made up of two different types of proteins. Each antibody contains two heavy-chain proteins and two light-chain proteins. There are five different types of heavy chains: IgG, IgA, IgM, IgD, and IgE. Determining which type of M protein (according to its heavy-chain and light-chain proteins) is in the blood or urine can help diagnose specific conditions. For example, about 50 percent of people with multiple myeloma have M protein made up of IgG proteins. The second largest group has IgA. IgM proteins are more often a sign of Waldenström macroglobulinemia.

Blood Tests

Some tests measure M proteins from blood samples. One such test is serum protein electrophoresis (SPEP). This test separates the proteins within a sample based on their electrical charges. SPEP shows changes in the levels of both M protein and other normal proteins. It reports the overall levels of M protein, but it doesn’t show what type of M protein a person has.

Immunofixation electrophoresis (IFE) tests may be performed along with an SPEP test. IFE shows what type of M protein a person has, but it doesn’t show the overall levels.

Blood tests may also include a quantitative immunoglobulins test. This test also determines the type of M protein found in the blood. A quantitative immunoglobulins test can measure the levels of immunoglobulin (Ig) G, IgA, and IgM. The test can help measure levels of both M protein and other normal immunoglobulins over time.

Another M-protein blood test is a serum free light chain (SFLC) assay. Although antibodies are made from both heavy- and light-chain proteins, plasma cells usually make more light-chain proteins. The extra light chains that aren’t used to make antibodies are released into the blood The SFLC assay measures these blood proteins.

Urine Tests

The urine protein electrophoresis (UPEP) test works the same way as the SPEP but uses a urine sample. Urine tests often also include tests for just the light chain part of the M protein. This is because the body eliminates extra-light chain proteins that are not attached to heavy proteins through the urine. When light-chain proteins show up in the urine, they are called Bence-Jones proteins.

UPEP involves collecting a sample of urine in a cup. Other tests may require a 24-hour urine sample, in which you collect all of your urine in a 24-hour period. Your doctor can give you further instructions if you need to take a UPEP or other urine test.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people with multiple myeloma and their loved ones. On MyMyelomaTeam, more than 16,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple myeloma.

Has your doctor told you that you have high levels of M protein? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

Posted on June 16, 2021
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Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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