Main content
What is Monoclonal gammopathy of undetermined significance (MGUS)?
Created by Matthew McPheeters.
Want to join the conversation?
- What exactly is the difference between MGUS and Leukemia? They are both monoclonal gammopathies of blood cells but Leukemia is a cancer and MGUS is not.(3 votes)
- MGUS and Leukemia are not equal. Leukemia is a proliferation of a particular line of blood cells. Gammopathies, like multiple myeloma or MGUS, are proliferations of a single, monoclonal line of antibodies. Multiple Myeloma is the malignant form, where the proliferation of a single antibody line causes systemic illness due to proliferation of plasma cells that make only that antibody. MGUS is usually an incidental finding that includes proteins that are of one antibody line. Unlike multiple myeloma or leukemia, there is no proliferation of plasma cells (or at least a very small number of them) within the bone marrow and the patient does not have lesions in the bone that we would expect to see with multiple myeloma. We don't know what causes this, nor do we know what it means, hence MG of undetermined significance. MGUS can only be diagnosed when all other hematologic diseases have been ruled out, including other leukemias.(2 votes)
- Aren't plasma cells B cells that can export antibodies into the lymphatic and circulatory systems? The B cells in the bone marrow are just that, B cells, not plasma cells or memory cells.
Would a plasma cell dyscrasia be like a B cell specific cancer?(3 votes)- The answer is "sort of". MGUS is asymptomatic and, by definition, NOT a cancer. Also, by definition, MGUS becomes multiple myeloma (which IS a cancer) when end-organ damage (evidenced by hypercalcemia, renal problems, anemia, and/or bone damage) appears.(2 votes)
- At1:16you talk about thrombocyte precursor cells. Are these also known as megakaryoblasts?
Are thrombocytes also known as megakaryocytes or are they different?
Thanks.(1 vote)- https://en.m.wikipedia.org/wiki/Megakaryocyte
Megakaryoblasts can divide,they are less mature than megakaryocytes. Once the 'blast' cell becomes the 'cyte' cell it performs the functions it is supposed to in the body, in this case the megakaryocytes enlarge and thrombocytes bud off from them and enter the circulation. Platelets and thrombocytes are interchangeable terms and they travel in the blood to form a plug if there is a hemorrhage. Megakaryocytes are their origin and they are huge cells that do not travel in the blood. Erythroblast and erythrocytes are another example of this use of terms, immature and mature cells within a cell line for red blood cells. Love words? https://en.m.wikipedia.org/wiki/Normoblast(1 vote)
Video transcript
- [Voiceover] Let's talk about monoclonal gammopathy of undetermined significance. Now, that's a little bit of a mouthful, so we're going to just refer
to it by it's acronym, MGUS. You'll also notice here that
I've separated monoclonal gammopathy from undetermined significance. I've done this because
I think it will help us to better understand
what MGUS actually is. Now, I'm going to start
with monoclonal gammopathy over here on the left. To do this, I'm going to go over a simplified explanation
of the pathophysiology of MGUS, as well as multiple myeloma. Both of these disorders
originate in the bone marrow. Let's draw a bone here. The bone marrow is the
central part of the bone. It's where blood cells are produced. I'm going to highlight
three types of cells that are located in the bone marrow. The first type are the
erythrocyte precursor cells. I'll draw those in red here. These erythrocyte precursor cells produce erythrocytes, which are also known as red blood cells. Next, I'm going to draw
in a few thrombocyte precursor cells, and the
thrombocyte precursor cells produce thrombocytes, which
are also known as platelets. Then, lastly, in green, I'm going to draw in the plasma cell precursor cells. They produce plasma cells. Now, it's important to
note that there actually many other types of cells
within the bone marrow that are not present in this drawing, but I'm only just highlighting these three types of cells in order to make the pathophysiology of MGUS
just a little bit more clear. Both MGUS and multiple myeloma are considered plasma cell dyscrasias. Dyscrasia is just another
word for dysfunction, so these conditions are the result of the dysfunction of the
plasma cell precursors. These plasma cell precursors
produce the plasma cells, and the plasma cells
then produce antibodies, which I'm just going to draw in here. Antibodies are a type of protein that are part of the body's immune system and help us fight infection. What happens in MGUS, as
well as multiple myeloma, is that for some unknown reason, certain individuals have
a monoclonal expansion of plasma cells. Now, what do I mean by this? Well, let's pretend we
have a plasma cell here. There's just a problem with one of these plasma cell precursors
here in that bone marrow. We'll identify that here
with just this one cell. There's a problem with this one cell. The other plasma cell
precursor cells are normal. But what happens when this cell replicates is it makes more dysfunctional cells, which then replicate and make
more dysfunctional cells. You can see here that this
one dysfunctional cell can produce, over time,
many dysfunctional cells, but they're all based off
of this one cell type. This process is known
as monoclonal expansion, mono, meaning one, so it
all comes from one cell, and clonal meaning replication. So you just have lots of
replication of one cell. We'll just draw that in here. All of these cells are
genetically identical because they result from one parent cell. This is where you get the monoclonal part of monoclonal gammopathy of
undetermined significance. Now, when you have this
monoclonal expansion, the replication rate of
this cell for some reason becomes unregulated, so it replicates much more frequently
than it normally would. With that, you get plasma cells that are producing a lot
more antibodies than normal. I mentioned before that these
antibodies are proteins, and these proteins can
be measured in the blood with a test known as
protein electrophoresis. A normal protein electrophoresis
looks something like this. It depicts the different types
of proteins that it measures, so this big spike here
correlates with albumin, which is the most common
type of protein in the blood. But then you also have these other categories of proteins,
which are known as alpha one, alpha two, beta, and gamma. What I'm going to focus here
is these gamma proteins. These gamma proteins
relate to the antibodies, so in someone who has
monoclonal gammopathy of undetermined significance
or multiple myeloma, you get all of these
antibodies that are identical, so on a protein electrophoresis you'll get a spike in this region that looks something like this. This is known as an M spike. The M stands for monoclonal. You get a spike in the gamma region, and this is why it's called a gammopathy. That's why you have a
monoclonal gammopathy. I mentioned that this same process occurs in MGUS, as well as in multiple myeloma, but what exactly is, then, the difference between the two of them? To go into that, let me
draw another bone here. Once again I'll put in our
bone marrow precursor cells. Up top here, in this top
bone, we'll have MGUS. Down here we'll describe multiple myeloma, which I'm just going to abbreviate MM. Now, in multiple myeloma, you also have this clonal expansion,
this monoclonal expansion, of one dysfunctional
plasma cell precursor, but the replication is even more so. It's even more unregulated, and so it kind of ends
up looking like this. What happens is the bone marrow becomes jam-packed with all of these dysfunctional plasma cell precursor
cells, and then it can't produce the other normal cells. So the big difference between
MGUS and multiple myeloma is that MGUS is more minor. These dysfunctional plasma cell precursors are occurring and they exist there, but you're still having normal production of red blood cells and
platelets and everything, and so you have no symptoms. MGUS is asymptomatic. In multiple myeloma, this dysfunction becomes so severe that
you start crowding out the bone marrow, and you have dysfunction of the other types of
blood cell precursors, and eventually someone
with multiple myeloma will develop symptoms. In this sense, MGUS is a
precursor to multiple myeloma. In fact, some people refer
to MGUS as pre-myeloma. From this pathophysiology,
you can actually get a better understanding
of what the symptoms of multiple myeloma might actually be. What happens is all of
these extra antibodies and proteins can result in renal failure, and then, like I mentioned,
these plasma cell precursors crowd out the bone marrow here, and you get a decreased
production of red blood cells, which results in anemia, and decreased production of platelets, which results in thrombocytopenia. Then also what happens
is these dysfunctional plasma cell precursors
produce some factors that cause the bone to be broken down, and so you get these
almost punched-out lesions in the bone, which are
knows as lytic bone lesions that I'm going to just
draw in here like this. The result of this, people
with multiple myeloma have lots of bone pain. As a result of this breakdown of the bone, the bone releases lots of calcium, and this results in hypercalcemia. These symptoms can be remembered with the acronym CRAB, C for hypercalcemia, R for renal failure, A for anemia, and B for bone pains. Let's just write that in here, CRAB. Because multiple myeloma
is this uncontrolled replication of these
plasma cell precursors, once it comes to this stage
and you have symptoms, it actually becomes a
malignancy or a cancer. If monoclonal gammopathy of
undetermined significance, or MGUS, is a pre-myeloma
and it can produce myeloma which is a cancer, why is that of undetermined significance? For many people you would
think if it's a precursor to cancer, that would be
of extreme significance. But, the reason it's
considered of undetermined significance has to do
with the rate at which MGUS becomes multiple myeloma. I want you to imagine a
group of 100 individuals who are 60 years old. Let's bring that in here. Once again, when we're starting here, they're all age equals 60. The reason I use 60 years old is because MGUS and multiple myeloma are most common in older individuals, especially above the age of 60. Now, the prevalence or the
percentage of individuals at age 60 who have MGUS is actually relatively high. It's somewhere between
three and six percent. That would be about five
of these individuals. Let's just pull five out here. Any random five. These five individuals have MGUS. Now, the important question to ask is not whether or not these five
have multiple myeloma, but the risk of which they will develop multiple myeloma over time. Let's imagine that these five individuals have lived to the average
life expectancy in the U.S., which currently is 78, but
we'll just make it easier, and we'll make them live
until they're 80 years old. Our question is, by age 80, how many of these five with MGUS are actually going to
develop multiple myeloma? The answer is just one. So although the prevalence of MGUS in individuals over the age of 60 is actually fairly high, somewhere around the percentage
of three to five percent, the rate at which they
develop multiple myeloma is actually pretty low. This rate is approximately
one percent per year. So MGUS is of undetermined
significance for two reasons. The first is that even
though the prevalence of MGUS is fairly high in
individuals over the age of 60, the chance that any single
individual with MGUS will develop multiple
myeloma is fairly low, meaning that they will likely
die of some other cause before they actually
develop multiple myeloma. Then the other reason it's
of undetermined significance is because it's very difficult to predict specifically which one
of these five individuals with MGUS is going to
develop multiple myeloma. So if you can remember that MGUS stands for monoclonal gammopathy of
undetermined significance, if you break down the
term you can remember that it is a monoclonal expansion of a single plasma cell precursor that produces large amounts of antibodies or proteins that result
in an M spike over here in this gamma region
of the electrophoresis, and that's why it's called a gammopathy. The significance is undetermined because it's asymptomatic
and it is difficult to predict what percentage
of those affected by MGUS will ultimately
develop multiple myeloma.