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Risk of MGUS Progression to MM

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A diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is challenging but determining your risk of MGUS progression to MM is the more serious issue in my experience. Is is common to live with MGUS for years.

I was diagnosed with a form of pre-myeloma in early 1994. At the time, there were no diagnostic tests to determing risk of progression to MM.

What are the signs of MGUS progressing to Multiple Myeloma?

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a condition in which an abnormal protein (monoclonal protein or M protein) is found in the blood. MGUS itself is generally considered a benign condition, but in some cases, it may progress to more serious conditions like multiple myeloma. High-risk MGUS is characterized by features that suggest a higher likelihood of progression. Signs of high-risk MGUS may include:

  1. High M protein levels: Higher levels of monoclonal protein in the blood may indicate a higher risk.
  2. Abnormal free light chain ratio: Measurement of free light chains (kappa and lambda) can help assess the risk. An abnormal ratio may be a sign of increased risk.
  3. Abnormal plasma cell percentage: An elevated percentage of abnormal plasma cells in the bone marrow may indicate a higher risk of progression.
  4. Non-IgG type of MGUS: MGUS can be classified into different types based on the type of immunoglobulin (IgG, IgA, or IgM). Non-IgG types, particularly IgM, may be associated with a higher risk.
  5. Abnormalities in other blood tests: Certain abnormalities in blood counts, kidney function, or calcium levels may suggest a higher risk.

Now, according to the research linked and excerpted below, if your bone marrow adipocytes density is decreasing, your risk of progression to full multiple myeloma may be increasing.

Because pre-myeloma- Single plasmacytoma of bone, monoclonal gammopathy of undetermined significance and smoldering multimode myeloma- are not cancer but forms of pre-cancer or pre-myeloma, conventional oncology has not developed therapies to reduce the risk of a diagnosis of multiple myeloma.

According to research, anti-angiogenic nutrition, supplementation and lifestyle therapies have shown the ability to reduce the risk of a full myeloma diagnosis. If you would like to learn more about these evidence-based, non-conventional therapies send me an email at- David.PeopleBeatingCancer@gmail.com 



David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma

“MM is preceded by a premalignant state known as monoclonal gammopathy of undetermined significance (MGUS), with a risk of progression to MM of 1% per year.

Establishing a scalable approach that refines the identification of MGUS patients at high risk of progression to MM can transform the clinical management of the disease, improve the patient’s quality of life, and will have significant socioeconomic implications.

Here, we provide evidence that changes in the bone marrow adipose tissue (BMAT) provide an early sign for progression from MGUS to MM.

We employed AI-assisted histological analysis of unstained bone marrow biopsies from MGUS subjects with or without progression to MM within 10 years (n = 24, n = 17 respectively).

Although the BMAT fraction was not different between the two groups, bone marrow adipocyte (BMAd) density was decreased in MGUS patients who developed MM, compared to non-progressing MGUS patients. Importantly, the distribution profile for BMAd size and roundness was significantly different between the two groups, indicating a shift toward increased BMAd size and roundness in MGUS patients who developed MM.

These early changes in the BMAT could serve as valuable early indicators for the transition from MGUS to MM, potentially enabling timely interventions and personalized treatment strategies. Finally, the AI-based approach for histological characterization of unstained bone marrow biopsies is cost-effective and fast, rendering its clinical implementation feasible…


We employed an AI-assisted approach to perform a systematic and objective histological characterization of the BMAT in progressing and non-progressing MGUS patients, with the aim of identifying possible BMAT features that were different between the two groups.

To facilitate translation to high-throughput clinical screening, we utilized unstained bone marrow biopsies by taking advantage of the tissue’s autofluorescence in the FITC channel (Figure 1A1C). We did not find a significant difference in the BMAT fraction within the bone marrow (% of total marrow) between the stable and progressing MGUS patients (Figure 2A). This suggests that the overall adipose tissue content in the bone marrow was comparable between the two groups.

However, we found decreased BMAd density in MGUS patients who experienced progression to MM compared to the non-progressing MGUS patients (Figure 2B). To gain deeper insight into the characteristics of the BMAds associated with MM tumorigenesis, we performed a morphological characterization of the individual BMAds. Importantly, we found a significant shift towards increased BMAd size and roundness in progressing MGUS patients (Figure 2C, 2D).

These observations suggest that during MM development, BMAds are subject to alterations which may be indicative of the disease progression. We and others have previously shown that BMAT is significantly reduced in non-treated MM patients [26, 27].

Lack of direct correlation between the bone marrow tumor burden and bone marrow adiposity in overt multiple myeloma, argues against the “space-constricted” mechanism causing decreased BMAT [26]. An alternative proposed mechanism is that cancer cells “hijack” the bone marrow metabolic programs to induce release of fatty acids from BMAds and fulfil their high metabolic demand [28].

It has recently been shown that induction of lipolysis and uptake of fatty acids by MM cells through fatty acid transporter proteins are involved in this process [28]. Therefore, it is possible that the shift towards increased BMAd size in progressing MGUS patients is an early sign that an altered metabolic program induced by MM cells has already started to take effect at this stage, leading to release of fatty acids from BMAds and disappearance of small BMAds, while exerting minor visual impact on the large adipocytes.”

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