What Is The M Protein And Why Is It Important?

What Does the M Protein Mean and Where Does it Come From?

What is the M protein?. Istockphoto.com/Stock Photo©extender01

Definition: M-Protein

The M protein is an antibody, or part of an antibody protein. Whole antibody proteins are called immunoglobulins. The M protein isn't just any old antibody, however.

In blood cancers such as myeloma, the 'M' in 'M protein' stands for monoclonal. A monoclonal protein is produced by the abnormal cells. It’s called a monoclonal protein because there is a single clone, a mono-clone, or a cellular legion of “identical-twin cancer cells,” all making this protein.

In the image, the Y-shaped blue antibody, or immunoglobulin, is the M protein. The big round object behind it is a plasma cell, which makes the antibodies. Not all M proteins are whole antibodies. Sometimes the myeloma's M protein is only one piece of an antibody.

Other Names for M Protein:

M protein can refer to different things, depending on what disease or topic you are discussing. In the context of myeloma, M protein refers to the abnormal product of your body's antibody-producing plasma cells. The M protein may also be described using terms as follow:

  • Monoclonal protein
  • Myeloma protein
  • Free immunoglobulin light chains
  • Paraproteins
  • Bence Jones proteins
  • The M spike
  • The M-component


Of note, there are several different settings in which the term "M-protein" is used in medicine. Here, we are talking mostly about the M protein that relates to cancer—and more specifically, to certain types of blood cancer and precancerous conditions of the blood and bone marrow.

But some other notable M proteins follow.

M Proteins Elsewhere in Medicine:

  • M protein may stand for viral matrix protein as in the M1 protein of the influenza virus
  • M protein may be used in referring to the bacteria streptococcus pyogenes
  • M protein, or actually protein M, is relevant the bacteria mycoplasma genitalia


    What is the M Protein in Blood Cancer?

    The M protein is an immunoglobulin or part of an immunoglobulin that is monoclonal, or produced by a single clone of problematic cells. It is not normal for the body to have so many copies of the exact same protein as generally occurs in myeloma, and this excess is detectable in laboratory studies. It can also cause problems in the body, especially if levels get too high.

    Where Does the M Protein Come From?

    In multiple myeloma, the M protein comes from a great excess of plasma cells. Ordinarily, plasma cells will produce a wide range of antibodies. Unlike the mass of abnormal, monoclonal identical twin cells, the normal, healthy state is to have cells capable of producing a diversity of antibodies—so-called polyclonal antibodies, or polyclonal immunoglobulins. When plasma cells become cancerous there is often only one very bad cell that has given rise to its minions. All of the minions are clones of the same cell, and they make only the same types of products - called a monoclonal proteins. Since there are a lot of plasma cells, multiplying abnormally, they make a lot of this monoclonal protein. Usually it is a whole antibody, but sometimes it's just a piece of an antibody.

    Structure of Monoclonal Antibodies 

    Each antibody is made up of four parts. There are two long chains on the inside, and two shorter chains on the outside. In the image, you can see a plasma cell with an antibody. In this case, all of the antibodies in the picture are the same. That is, they are monoclonal antibodies.

    The light chains, or the shorter, outside lines in the blue Y in the picture, are also called a Bence Jones proteins, or free immunoglobulin light chains. When the M protein is a light chain, it is small enough that it passes through the kidneys, sort of like small things slipping through the strainer, so that the body does not retain them, and they pass into the urine.

    So, if you only look in the blood, you can miss light chains. If the M protein is a whole immunoglobulin—the whole big Y in the picture—then it can will be detected in the blood, since it is too large to pass to the urine. Because these large proteins are retained, excessive buildup of such M protein in the kidney can cause kidney disease.

    Importance of the M Protein

    There are a few reasons that the M protein is significant:

    • Diagnosis - The M protein is often found in multiple myeloma and several other conditions 
    • Kidney damage - When M proteins are big enough and plentiful enough in the case of malignancy to clog the functional units of the kidney, this can lead to kidney disease and ultimately kidney failure.
    • Depending on the characteristics of the secreted protein, other harmful effects are possible.

    Blood and Marrow Conditions With an Increase in M Protein

    Conditions that may result in an elevated level of M proteins on a urine test include:

    • Myeloma - A urine test will be positive for M protein in 50 to 80% of people with myeloma.
    • MGUS - Monoclonal gammopathy of undetermined significance may have an elevated level.
    • Waldenstrom's macroglobulinemia - This cancer, which involves cells which are precursors of plasma cells, may have an elevated M protein level.

    In some cases, same process causing the M-protein is malignant, and the malignancy may invade the bone, lymph nodes, liver, spleen, or other organs. This is the case in multiple myeloma, solitary plasmacytoma, and Waldenström macroglobulinemia. In other cases, the M-protein is produced by a small limited premalignant clonal expansion, and causes no symptoms. This is the case in monoclonal gammopathy of undetermined significance MGUS.

    Other conditions:

    Many conditions can cause a monoclonal gammopathy, a spike in one protein product; not all of these conditions are cancerous. You can have M protein with certain connective tissue disorders, like systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. You can have it with Hepatitis C virus infection and HIV/AIDS. You can even have it with acquired von Willebrand disease, a rare bleeding disorder.


    Leukemia and Lymphoma Society. Diagnosis. Accessed 03/01/16. https://www.lls.org/disease-information/myeloma/diagnosis

    Papanikolaou X, Rosenthal A, Dhodapkar M, et al. Flow cytometry defined cytoplasmic immunoglobulin index is a major prognostic factor for progression of asymptomatic monoclonal gammopathies to multiple myeloma (subset analysis of SWOG S0120). Blood Cancer Journal. 2016;6(3):e410-.


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