This week there are several interesting items in the news that help us understand how and why monoclonal gammopathy of undetermined significance (MGUS) occurs, and when it may or may not turn into active myeloma.
Matthew Drake and the Mayo Clinic bone research team worked with a group from Sheffield University in the UK to illustrate that the bones in MGUS patients are not normal. MGUS patients have weakened bones versus age and sex matched controls. There is increased porosity ("more holes") in surface bone and reduced bone strength. This is important and at the same time quite puzzling. It is important since we now need to be looking more closely at this to assess if bone treatments, such as we use in active myeloma, need to be considered also for MGUS patients. But the puzzling part is that we associated bone problems with the "B" in "CRAB," features characteristic of active myeloma.
So we need a new level of scrutiny about the type and severity of bone damage that indicates transition to active myeloma. These indicators are: a positive PET/CT scan; definite lesions on a whole-body low-dose CT scan, and or/multiple lesions on an MRI scan. Just reduced bone density is not specific enough or sufficient. This is certainly not the end of the story in terms of understanding what is happening in MGUS versus the major change that occurs with serious bone destruction in active myeloma.
Another interesting story that caught my attention is the report of the full genetic sequencing of sharks that have cartilage, but no true bone like humans. It turns out that sharks are completely missing all the genes needed to make bone. It also turns out that they are also missing genes linked to the immune and blood system which are part of the same complex. What you may not know is that sharks rarely develop "bone" cancer (such as myeloma). It was thought that this was because cartilage blocks cancer formation.
I carried out research years ago which revealed that there is some evidence for this idea. If you add cartilage components to myeloma cultures, growth of the myeloma is slowed - a little, but not a lot. Despite this there was a phase of great enthusiasm about "shark cartilage" treatments. And some short-term benefits were seen. But now it is clear that sharks lack hard bones and also lack the cells that can link in with myeloma cells to increase myeloma cell growth. Having hard strong bones is excellent. But these bone cells, if triggered the wrong way, can lead to bone destruction, immune defects, and ultimately myeloma in some cases.
Our old ideas have been turned upside down! It is not the presence of cartilage which makes the difference, it is the absence of bone cells.
Triggering the activity of the myeloma cells is the key aspect of myeloma and true bone destruction. A study from the Swedish team shows that increased Freelite levels are still a reliable indicator of disease progression to active myeloma. Yet another study looking at the overall cell genetics shows that many genes are involved in the activation of MGUS and the predisposition to MGUS in the first place.
So, lots of things in the news. Always many new things to learn. Every new detail allows us to understand better and guide patients with critical decisions for recommended diagnostic testing and treatment choices.
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