Three blood samples with varying numbers of proteins in them

MGUS and the Multiple Myeloma Connection

Last updated: December 2022

Monoclonal gammopathy of undetermined significance (MGUS) is a medical condition characterized by increased levels of M protein in the blood. M (monoclonal) protein, also called a paraprotein, is produced by plasma cells. Plasma cells produce antibodies called immunoglobulins, which are proteins that attack foreign invaders and help the body fight infections.1,2

How does MGUS develop?

Plasma cells grow in bone marrow. In the normal process of white blood cell growth, plasma cells produce a variety of antibodies that can attack many different kinds of infections. Sometimes plasma cells produce an excess of immunogobulins leading to MGUS.

How common is MGUS and what are the symptoms?

MGUS is a condition that may never produce any symptoms. One of the more common symptoms of MGUS is burning or tingling in the hands and feet. This is called peripheral neuropathy. MGUS has also been associated with other conditions such as osteoporosis and venous thrombosis, as well as with people who have a compromised immune system.

MGUS affects about 1% of the general population. Incidence rises as you age, although it is still low. Risk rates are around 3% of people over age 70.3 The risk is double for veterans who have been exposed to Agent Orange and other chemicals.1

How is MGUS diagnosed?

A diagnosis of MGUS is generally made when results from routine blood tests show an increase in protein levels. Your doctor may request additional specialized blood tests, called serum electrophoresis, which can identify the abnormal antibodies found in the blood. Urine tests can evaluate whether any excess protein is spilling over into the urine. Some additional tests, including x-rays, scans and bone marrow samples, may also be requested.

A primary care physician can monitor MGUS with periodic blood and urine tests. This will monitor for any changes in the protein levels in your blood. Treatment is generally not necessary for MGUS if there are no changes to the protein levels and you are not experiencing any symptoms. Monitoring of serum protein levels several times a year allows physicians to look for any changes that would indicate a risk for a more severe condition. Many people live a long life with MGUS without ever developing serious symptoms or progressing to a more serious condition.

MGUS and multiple myeloma

MGUS can be a precancerous condition. It can progress to different kinds of blood cancers including multiple myeloma and lymphoma.1 Around 20% of people who have MGUS will eventually develop a malignant plasma cell cancer, such as multiple myeloma. Almost all cases of multiple myeloma begin with MGUS.2

Multiple myeloma develops when a normal plasma cell mutates, or changes, into a myeloma cell. These myeloma cells can grow uncontrollably and develop into tumors inside and outside of the bone marrow. The disease is called multiple myeloma because tumors develop in multiple locations within the body. As the myeloma cells grow, they displace and break down good blood cells, like white blood cells that fight infection and red blood cells that carry oxygen throughout the bloodstream.

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