_MG_stain.jpg "Myeloma bone marrow aspirate smear")
Q. Here’s a question from Twitter: Can you explain to me what the M protein in multiple myeloma is?
A. Multiple myeloma is a malignant, clonal disorder of plasma cells that originates in the bone marrow. It’s a relatively common disorder, accounting for 1% of all malignancies and 10% of all hematologic malignancies in adults. Patients present with painful, lytic lesions of the bones, recurrent and persistent infections, weakness, renal failure, and hypercalcemia. The prognosis is generally not great, but new chemotherapeutic agents seem to hold some promise.
Patients with myeloma have a monoclonal proliferation of plasma cells in the bone marrow, meaning that there are a ton of malignant plasma cells that all originated from the same initial cell. In the bone marrow aspirate above, you can see tons of malignant plasma cells. A few look a lot like plasma cells, with clock-face chromatin and a hof and everything, but others look for all the world like blasts. That’s one thing to remember about myeloma – malignant plasma cells don’t always resemble their nice little benign counterparts.
The malignant plasma cells almost always secrete immunoglobulin, and because they are monoclonal, they all secrete exactly the same form of immunoglobulin. This is very different than what you see in a patient without myeloma, where there are a bazillion different types of plasma cells, all making different types of immunoglobulin molecules. This huge mass of all-the-same immunoglobulin secreted by myeloma cells is called a “monoclonal gammopathy;” the normal immunoglobulins are called “polyclonal.”
Monoclonal gammopathy is so characteristic of myeloma that you can use it for both diagnosis of disease and follow-up of patients. You can detect the monoclonal immunoglobulin using serum electrophoresis (which separates the blood proteins into groups based on charge and size). There’s a predictable pattern of proteins in normal serum: albumin (the most abundant protein in the blood) migrates to a certain predictable point; other proteins migrate to different places (which are given different names – the alpha 1 region, the alpha 2 region and the beta region). Immunoglobulins migrate to a unique place called the gamma region, and because they are all different (in normal patients), they migrate to slightly different places within that region, giving a gentle bell-shaped curve or smear (depending on whether you’re looking at a tracing or the actual bands on the gel).
In myeloma, the immunoglobulin is monoclonal, so it all migrates to exactly the same spot on the gel! Which gives you a big spike (if you’re looking at a tracing) or a very distinct, crisp, strong band (if you’re looking at the gel itself). This spike is called an M-spike (you could remember M for either monoclonal or myeloma), and the corresponding monoclonal protein that it represents is called an M protein.
A few other things to note about this M protein:
1. You need to do electrophoresis on urine too, not just serum. Some cases of myeloma secrete only light chains (these are called Bence-Jones proteins), which are so small that they are passed in the urine (so if you only looked at the blood, you’d miss them).
2. While patients with myeloma have an increase in the total amount of immunoglobulin present in the blood (due to the large monoclonal immunoglobulin spike), they also have a decreased amount of normal, polyclonal immunoglobulins. So when you look at an electrophoresis, you’ll see this huge spike in the gamma region, but also a noticeable depression in the amount of the background normal immunoglobulins.
3. A little trivia regarding the kinds of immunoglobulin expressed by myeloma cells. The most common heavy chain expressed in myeloma is IgG (60%); next is IgA (20%). Rare cases express IgD or IgE, and IgM myeloma is virtually nonexistent (most cases of plasma cell lesions that express IgM turn out to be Waldenström macroglobulinemia). Almost one-fifth of all cases of myeloma secrete only light chains. And somewhere between 1 and 5% of all cases of myeloma secrete no detectable immunoglobulin at all! Which, without the familiar M-spike, would make for a pretty difficult diagnosis.
loveliest blog I’ve ever found!!
you can also found a M-spike in a Bening condition called MGUS= Monoclonal Gammopathy of Undetermined Significance
Another piece of trivia: people are often confused by the fact that the disease is “multiple” myeloma and there is a monoclonal protein or M-spike. The name actually came form the multiple bone lesions seen on x-ray in this disease.
Yes, Mary – exactly right! There are multiple tumors (“-oma”) in the bone marrow (“myelo-“) in this disease. Thanks for pointing that out.
Best explanation of a very diverse topic. New at oncology but old nurse. Thank you for the “down to earth” explanation. Keep up the good work 🙂
This might be the best read i’ve seen all day (studying for boards :-/ ) Thanks, this blog is already bookmarked!
I have MGUS so I am very happy to see a good explanation of the M Spike.
Thank you for making learning so much fun and animated. This blog is real blessing !!
Thank you for making learning so much fun and animated. This blog is a real blessing !!
Excellent site and excellent elaborations !
I have MM and recent bone marrow biopsy showed a 75% reduction in plasma cells from one year ago. Wondering..does anyone know if there is a correlation between the Total Protein in SPEP blood test and the M-Protein (as the Total Protein goes down does it relate to the M-Protein).. Hope this is not confusing..
Glad to hear your plasma cells are decreased! Yes – there is a relationship between the total protein in the blood and the M-protein. The total protein in your blood includes all proteins: albumin (which is the most abundant), immunoglobulins (including monoclonal immunoglobulins – or the M spike – if there are any), and a bunch of other proteins. If you had a large M spike, your total protein would go up. As the M spike decreases, your total protein should decrease too (but never to zero, since you still would have the other, normal proteins in your blood). Hope that helps.
Nice explanation. Thanks… MS1 studying for head and neck final 🙂
great explanation. thanks a lot!
Dr. Krafts gives a GREAT explanation ofM-spike. Succinct, complete, and colloquially entertaining! I’m and MD-JD who graduated med school in ’86 and has practiced Internal Medicine for 22 years. This is the best explanation I’ve seen. You are to be congratulated.
Thanks for explaining so a layman can understand. My sister is seeing an oncol for the first time after finding protein in the urine and low levels of blood antibodies. We are hoping for the best tomorrow. We hope the prognosis os positive. Again…thank you.
Alan
Chicago, illinois
Thank you so much for this info. My husband and I visiting Oncol today for diagnosis after bone biopsy. This will aid us in understanding what the MD will most likely feel is beyond our knowledge base.
Thank you so much!! I’m a Nurse for 8 years and in my last year of studying for nurse practitioner. Working in clinical setting with an excellent internal medicine Dr. When I see something I’m not sure about I look it up, lucky me I found your blog!
what is the normal range for an M-spike
Any M-spike is abnormal – so there isn’t really a reference or normal range. An M spike can be as large as it wants! It might be helpful to remember that myeloma tends to produce a monoclonal spike over 3 g/dL, whereas the diagnosis of monoclonal gammopathy of undetermined significance requires that the monoclonal spike be less than 3 g/dL.
My husband had blood tests done which showed a high Gamma Globulin of 2.1 and an M-Spike of 1.7. He was relatively inactive for 2 years due to hip pain and had a hip replacement a few months ago & NUMEROUS x-rays during the last year, from both MD’s and Chiropractors. He now feels great & is able to be active without any pain. He has some tingling in the bottom legs, which has been diagnosed as neuropathy. The MD who ordered this blood work wanted to proceed with x-rays, biopsy, etc, without really understanding what had gone on in the past year. We are inclined to wait for 6 months & have the blood work done again before we proceed with any other tests. Even if we had tests that confirmed multiple myeloma, we understand there is no cure……………..so why even have further tests?
Hi there –
Thanks for sharing your story. I’m so sorry to hear about your husband’s illness. It is always a good idea to consider what you would do with the information you’ll get from tests. You’re right – if you’re not going to do anything with the test results, why do the tests?
While there is no real “cure” for myeloma, there are new drugs that have come out within the past few years that can be very helpful. These drugs have helped a lot of patients live more pain-free and active lives. I think if it were me (or my husband) I would proceed with getting a few tests to establish whether he has myeloma (or whether it’s something else). That way, you can decide what type of treatment, if any, you’d like to proceed with. At least then you’d know where you stand.
That’s just my opinion though – it’s really a personal thing, and you and your husband should do what you feel in your hearts is the best.
I hope that helps a bit! Feel free to email back if you have other questions. Best of luck and sending good thoughts your way.
Kristine
My mom was diagnosed in 2006 with MM. She has the type that shows up in her urine, the Bence Jones protein. She had success with Velcade treatment for years and then had a stem cell transplant in November of 2010. She maintained under a 5% myeloma in her bone marrow until August of this year, 2012. After finding out it was back she decided to go in on a study being done at Mayo in Rochester. It is a treatment of Velcade and the new study drug, pomalidomide. She had her tests done and on August 29th her total protein in her urine was 8178 and yesterday we went in for her check up and it was down to 89! Her M spike had been at 7020 and it was down to zero! We are very thankful.
WOW! I’m so happy for you!! Myeloma can be a tough disease to beat – but the newer drugs are SO much better than the ones from years past. Hooray!! Thank you for sharing your story with us.
Thanks so much. This is extremely helpful.
So If I have none detected ,would it be normal??
Correct – you should not have an M spike. You should have immunoglobulins, of course – but they should be in the shape of a gentle curve, not a spike – because normal immunoglobulins are all slightly different (so they migrate to slightly different places within the gamma region).
I had a tick related infection 6 weeks ago. The infectious disease MD did a serum protein electrophoresis and a random urine electrophoresis. An M-spike in the urine resulted as 14.9. None in the serum. He wants me to see an oncologist based on this one result, mainly because my brother died of MM at age 51 in 2002. Is he over reacting?
Sorry to hear about your sickness. No, I don’t think he’s over reacting. Any monoclonal spike should be investigated – because it’s an abnormal finding. The fact that your brother had myeloma is potentially related – but even in the absence of a family history, I would have that investigated. Some types of immunoglobulin (specifically, those that are composed just of light chains) are excreted in the urine (so you won’t see them in the blood). Let us know what happens – my thoughts are with you!
Thank you this easy-to-understand information!! I just got test results back with my M-spike going from 1.8 to 2.0 in a year and a half. My next appointment/check is in 3 months. I have a question. Are there a list of the new drugs to treat MM? What are their side effects? Do they replace a stem cell transplantation or accompany it? Thank you once again!
There are definitely new drugs that are being used in multiple myeloma. Some of these drugs are specific for the myeloma cells (as opposed to traditional chemotherapy, which just kills dividing cells in general), which is a huge improvement – better at targeting the cancer cells and less likely to cause side effects. Not being a clinician, my knowledge is pretty limited on these drugs – but I am sure that your oncologist will be up to date on all the new drugs, and their side effects, and whether they are best used before, during, or instead of a stem cell transplant. I do know that the prognosis for myeloma has improved drastically in the past several years due to these new drugs – so there is hope! Ask everything you want to ask (maybe write it down so you don’t forget once you get to your appointment) – and if you don’t get answers, or don’t feel listened to, then I would recommend you get a second opinion. You deserve to know everything that’s available, and you deserve to have all your questions answered! Best wishes to you.
My son has been ill for about 3 years. No doctor has been able to diagnose him. He got on the internet and demanded a test specific for lymphoma. The doctor finally did a urine analysis and a 24 hour urine. He also had a lower back x ray recently and it came back OK but they found what they thought were cysts on the kidney. We don’t have the results of that yet. However, he did call the Dr. and the nurse told him that they urine test showed an M spike of 8.5. I now understand from your blog that this is significant for mm. Are there any other less fatal causes for this high of a spike? He is 52 years old. I would appreciate your help. Thank you. MJ
Hello.
I am a 25 year recipient of a cadaveric kidney transplant. I also received Hepatitis C (HCV) from the transplant and am at stage 3 portal fibrosis. I have been immunosupressed for the entire period with Cyclosporine, Cell-cept, and Prednisone and have undergone an unsuccessful course of Interferon and Ribavirin therapy for the HCV. On my previous two blood tests I showed elevated Calcium levels so my Nephrologist did a lab workup for Secondary Hyperparathyroidism (SHPT) and pre-cancer screening. The results showed an M-spike of 2 g/dL and I was referred to a hematologist. He recommended that the Momoclonal Gammopathies (among other things) be monitered every three months. Being fairly well versed in how easily good things can go bad I concurred (I also hate bone marrow biopsies).
I appreciate the information provided in this blog and comment section greatly. As to what I will do with any significant negative changes, all I am willing to say is that the quality of my future life on Earth is far more important to me than enduring yet another disease and treatment regimen. I have been blessed with a good, yet undeserved, life. There truely is, however, a time to let go. I am 57. ds
Hi All!
It has been a very difficult journey for me. I’m a disabled veteran, and in 2010, I was having bone pain, polyneuropathy in legs, arms, back and hip- bone pains and complained this to my Dr. which he told me nothing! Just wanted to give me more medications for the pain!
Luckily, I had an appointment with the neurologist and he listened and conducted the SPEP test that showed 2 abnormal gamma bands. After the appointment, Neurologist called my doctor and all of a sudden, my primary care doctor stated I had MGUS and never called me!
A month later, I ordered my medical record he stated in my record that I had MGUS for ten years but never informed me of this. When I did meet with him, he stated that I had nothing to worried about and I’m in the process of changing this doctor.
The (VA) veteran medical hospitals have some very good doctors and others that do not know what they are doing or just don’t want to refer their patients to other drs. I hope this is not confusing to you all! I look forward to hearing from you all. I’m glad that I found this site.
Thank you!
Frank
Can we find the plasma cells involved in a blood smear?
No – myeloma virtually never involves the blood for some reason. You can detect the M-spike in the blood – but the plasma cells stay in the marrow.
I’ve been under the care of oncologist for 10 yrs now, have had 2 tumors, one very large tumor in the left femur 8CM, due to extremely stron radiation the hip finally fractured & i had 2 surgeries in the winter of 2008, possibly having a 3rd, hardware seems to be coming loose. I have M spike, also MGUS. My last tumor was in my spine & we did radiation to it & it’s gone. Thnk God. about to see my new emory oncologist in 2 days, doing the 24 hr urine test as I type, so far every time Ive done this urine test, it comes back clean. So for me it’s been 10 long years of tests, biopsies, radiation therapy, 2 yrs of chemo for CLL leukemia, but I try & stay positive because I feel very blessed that so far they have not been able to give me a definite diagnosis of MM. Praise God again. I just happened on this site looking up some of my blood test, as though I know what I’m reading. My oncologist, has explained to me that with my history &the fact that I’ve had 2 cancer tumors, it is almost a 100 % that it will be diagnosed with MM eventually, that no one gets tumors w/out a cause. She explained to me that tumors in the bone start in a primary place first. So they watch me closely. BUT I chose to be positive & trust in GOD. That he is in control & not me nor the Dr’s. Can it be scarey @ times, of course. I’m human. right. But I think for me, I don’t dwell on this fact, I continue to work a full time job & have a very busy life. God Bless everyone out there struggling with this illness, BUT keep your head up. There is HOPE. Cancer is NOT what is used to be 15 yrs ago, I know I lost both of my parents within 6 weeks of each other, BOTH to Cancer, colon & lung. So times are better for all of us now. God Bless All
Hi Janice –
Thanks so much for sharing your story with us. It’s really important to hear about what patients go through with their diseases. I wish you the very best and will keep you in my prayers.
I have the m Protein but normal bone marrow. What does that mean?
Thanks for writing in, Lynn. If you have an M spike (or M protein), that means that you have a population of plasma cells that are all making the exact same type of immunoglobulin. This happens in multiple myeloma – but it also happens in something called monoclonal gammopathy of undetermined significance (MGUS), and in other, less common, plasma cell or lymphocyte disorders. Having a normal bone marrow biopsy is always good. This may mean that your M spike is due to MGUS – particularly if you don’t have symptoms (like bone pain, renal failure or fatigue). There is a chance that the biopsy may have missed a population of myeloma cells in your marrow – but that is unlikely. Your doctor will probably want to follow you, and monitor your M spike to see if it stays the same or goes up. If it goes up suddenly, or gets to be very large, that would be worrisome. Best wishes to you!
Kristine, thanks so much! I’ ve been really confused by the results. I am going in for a ct scan next week. I guess that may help rule some things out. Lynn
OK, I’m just beginning this journey…I haven’t even had a bone marrow biopsy done yet. The doc thinks that I do have some level of multiple myeloma, though…whether it’s MGUS or ‘smoldering myeloma’ or the full blown thing, we don’t know yet. The blood tests so far are….shoot, I don’t know! The point is, I’m an English teacher, not a health professional, much less an oncologist! I can do research, but all the articles I’ve seen so far can’t figure out whether they should be full of unintelligible jargon or Pollyanna simplism. This article, though, is informative, clear, and uses measurements, ideas and concepts I can understand and follow.
Don’t give me the metric system. I’m just fine with ‘tons’ and ‘bazillions!”
Thanks for joining us Diana! I’m sorry to hear you have abnormal blood tests – it’s so nerve-wracking to go through all the tests and waiting. Let me know if there’s anything I can do to help – maybe I can help decipher some of the medical terms. Best wishes to you!
What a great site!!! Thank you SO much!!
My sister was recently diagnosed with MM. The doc told her her level was 600+ before treatment and now after one cycle of chemo it is down to 200+ he did say the normal was 1.7, could these numbers represent her M-spike, seems rather high, did anyone else have really high numbers like these when first dx.
No – that’s way too high. Maybe the units were different – 6.00 down to 2.00 or something (sometimes results get changed a bit in translation).
I love your blog. So helpful to patients as well as pathology students.
That said, I have Waldenstrom’s Macroglobulinemia (MM’s nicer cousin, so to speak, which presents with WM’s typical high monoclonal IgM).
On my spep results, it shows an M-spike number and right beneath that is shows an M-spike%. For instance:
M-spike: 0.89 g/dL
M-spike%: 13.04
What is that M-spike% a percentage of? Can’t find an answer anywhere on the web for this question, so maybe you’ll be kind enough to enlighten me?
Hi Penny –
I’m sorry to hear about your disease – you’re right, it’s “nicer” than myeloma – but still not fun.
The M-spike percentage is the percentage of the total protein that is made up of the M spike. Your total protein must be about 6.82 g/dL – because 13.04% of 6.82 g/dL is 0.89 g/dL. I think it’s just another way to follow the magnitude of the spike – though I think the size of the spike itself (the 0.89 g/dL) is probably a more direct and useful way of following it. Hope that helps!
The M.Spike that I’m familiar with is reported as a number. In this case usually 1.3 or 1.4, i.e. stable over 2 years.
question: what units does the 1.3 or 1.4 represent? and what is the range of the M.spike values?
Thank you for a very helpful website and discussion.
Lebon
The units are grams/dL (grams monoclonal antibody per deciliter blood). Any M spike is abnormal! You should not have any monoclonal antibodies in your blood. Not all M spikes are malignant (a fair number represent MGUS) though. So there’s no real “normal” range for M spikes. One number that you might want to know is 3 g/dL. An M spike above that number is highly suspicious for myeloma (or another malignant process).