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At UT Southwestern, we adopt a comprehensive and patient-centered approach to managing precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS).

Our dedicated Monoclonal Gammopathy Precursor team provides personalized monitoring and care to help with early detection and optimal outcomes.

What Is MGUS?

MGUS is a condition marked by the presence of an abnormal antibody in the blood. This antibody, known as a monoclonal protein, or M protein, is produced by plasma cells, or B lymphocytes, typically in the bone marrow. MGUS is present in roughly 3%-5% of the population above age 50.

MGUS can lead to more severe conditions, with the most common being multiple myeloma, a blood cancer of the plasma cells. MGUS can also lead to lymphomas such as Waldenstrom macroglobulinemia, AL amyloidosis, and monoclonal gammopathies of clinical significance (MGCS).

Because of this risk of progression, MGUS is called a precursor condition. It is generally considered precancerous, though MGUS itself is benign. And while it’s important to monitor MGUS, it usually doesn’t progress into a more serious disease. Most patients will not develop multiple myeloma or another blood cancer.

UT Southwestern’s Monoclonal Gammopathy Precursor (MGP) team helps patients receive accurate diagnoses and personalized monitoring based on the latest medical guidelines. Our goal is to detect any changes early, provide peace of mind, and offer proactive care that aligns with each patient's needs.

Our team includes renowned specialists trained by prominent leaders in myeloma and monoclonal gammopathy research. This depth of expertise allows us to provide leading-edge treatment and management strategies.

What Are M Proteins?

Monoclonal proteins, or M proteins, are abnormal antibodies. They can be found in the blood or urine. Like all antibodies, M proteins are made by white blood cells (specifically, plasma cells and B lymphocytes) that live in the bone marrow. When these white blood cells become altered, they don’t stop making antibodies. Instead, these cells begin producing abnormal antibodies, which are detected as M proteins.

M proteins, like all antibodies, have different types of “heavy chains” and “light chains.” The most common types of MGUS are IgG kappa, IgG lambda, IgA kappa, IgA lambda, IgM kappa, IgM lambda, and free light chain.

The presence of an M protein is necessary for MGUS and all monoclonal gammopathies.

What Causes MGUS?

Normally, plasma cells and B lymphocytes in the bone marrow produce the antibodies that circulate in our blood. MGUS occurs when a group of plasma cells or B lymphocytes in the bone marrow undergo cellular changes. The exact causes of this are not well understood, but changes in the genes of plasma cells and lymphocytes might play a role. As with most precursor conditions, the causes of MGUS are an active area of research.

Several factors may increase the risk of developing MGUS or a related monoclonal gammopathy:

  • Age: The condition is more common in older adults, especially those over 70.
  • Race: African Americans and people of African descent have a higher risk of developing MGUS compared with other ethnicities .
  • Sex: It is more common in men than in women.
  • Environmental exposure: Being around certain chemicals, such as pesticides and industrial solvents, may increase someone’s risk.
  • Family history: Having close family members with MGUS may raise the likelihood of developing the condition.
mgus symptoms - monoclonal gammopathies of clinical significance

What Are the Symptoms of MGUS?

Most patients with MGUS don’t experience any symptoms, and the condition is often discovered by chance during routine blood tests for other reasons.

In some cases, patients might develop symptoms related to complications of monoclonal proteins, which can include:

  • Bone issues: Increased risk of osteoporosis and fractures due to decreased bone mineral density
  • Nerve problems: Numbness, tingling, or neuropathy resulting from nerve damage
  • Kidney problems: Signs of renal impairment without other identifiable causes
  • Infections: Higher risk of infections, as MGUS can weaken the immune system

These symptoms are not caused by MGUS itself but are due to other monoclonal gammopathies such as monoclonal gammopathies of clinical significance (MGCS), AL amyloidosis, and other disorders that can arise from MGUS.

A closely related but separate condition is smoldering multiple myeloma. This is when the M proteins and the cells that make them have advanced beyond MGUS to become cancerous as multiple myeloma, but there are no symptoms. As a result of this stage being undetectable until is cancerous, smoldering multiple myeloma is usually not treated.

How Is MGUS Diagnosed?

MGUS is typically diagnosed through routine blood tests that detect abnormal levels of M protein in the blood. Since it usually doesn’t cause symptoms, the abnormal protein is often found incidentally.

Further diagnostic steps may include:

  • Blood tests to measure the level and type of M protein, assess other antibody levels, and check kidney function and other organ systems
  • Urine tests to check for the presence of M proteins in the urine over a 24-hour period
  • Imaging studies, such as X-rays, magnetic resonance imaging (MRI), or positron-emission tomography (PET) scans, if bone pain or lesions are suspected
  • Bone marrow biopsy to determine the makeup of plasma cells and lymphocytes and to rule out multiple myeloma or other blood cancers

These evaluations help differentiate MGUS from more serious conditions and establish an appropriate monitoring plan.

How Is MGUS Treated?

MGUS itself doesn’t require specific treatment, but regular monitoring is essential to detect any progression to more serious conditions such as multiple myeloma. By closely following patients, we can initiate treatment promptly if progression occurs, helping to provide the best possible outcomes.

Patients should undergo periodic checkups, typically every six months to 12 months initially, to monitor the levels of M protein and assess for any changes that might indicate progression.

If MGUS leads to complications such as kidney disease, anemia, or other issues, a broad workup is pursued to ensure that the MGUS has not progressed to a more serious monoclonal gammopathy such as multiple myeloma.

What Support Services Are Available for Patients with MGUS?

UT Southwestern Medical Center’s Harold C. Simmons Comprehensive Cancer Center offers extensive support services for patients, including:

Does UT Southwestern Offer Clinical Trials for MGUS?

UT Southwestern’s MGP Clinic actively participates in research and clinical trials, contributing to advancements in understanding and treating multiple myeloma and related monoclonal gammopathies. Ask us for more information.

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