Published on April 8, 2014
Dr. Srdan Verstovsek, a world-renowned expert at MD Anderson Cancer Center in Houston, defines the three types of MPNs (myeloproliferative neoplasms): essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). He goes on to explain how clinicians differentiate between the types of MPNs in order to make an accurate diagnosis.
The Ask the Expert series is sponsored through an education grant to the Patient Empowerment Network from Incyte Corporation.
Transcript | What Is an MPN?
MPNs and What the Three Types Are
What is an MPN, and how do you differentiate between ET, PV and myelofibrosis?
In the bone marrow, this is the soft tissue inside the big bones that makes cells, there are problems that may develop over time. And there are two major problems that we classify in two different large groups of diseases, myelodysplastic syndromes and myeloproliferative neoplasms. Dysplastic syndromes, dysplastic means out of shape. That's on the side. The focus is on myeloproliferative. Myeloid stands for the bone marrow cells. Proliferative, growing without control. So maturation process from the baby cells, blast, to normal white cells, red cells and platelets is out of order, and you get abnormalities in blood cell count.
Many subtypes of MPNs derive their names from what is wrong with the blood. In terms of having high platelets and everything else is normal, this is usually called essential thrombocythemia, ET. If all the cells grow without control in the blood and you have many red blood cells, that's called polycythemia, polycythemia vera. Many of these patients also have high vitals and platelets.
The unusual type is myelofibrosis. Myeloid, again, bone marrow cells. Fibrosis is derived from the bone marrow. This is where the malignant cells in the bone marrow grow, but the environment, the cells that support the growth of these malignant cells, so?called stroma or stromal cells, secrete some proteins, that's what we think how it happens, leading to the formation of the fibers, the scar tissue, like when you develop a scar tissue on the skin when you cut yourself.
This is a reactive process, we believe, to growing malignant cells, and the bone marrow becomes fibrotic. Scar tissue develops, limiting the growth of the cells. In more often than none, the patient with myelofibrosis will present too few cells in the blood. One of the typical problems with myelofibrosis is not too many red blood cells, it's too few. Patients are anemic. Patients still may have a high white blood cell count or high platelets, but many have low white cells and low platelets.
Many develop very big spleen. Because of the failing bone marrow we think the spleen is enlarging, being a blood organ, and trying to, maybe, make some blood. The liver can enlarge. Body wasting happens and a lot of symptoms. That's more aggressive disease.
Now how do you dissect between ET, PV and myelofibrosis knowing also that that's a spectrum of a myeloproliferative neoplasm and patients can change from one to the other? Know that today I have ET, tomorrow I have PV, or today I have ET tomorrow I have myelofibrosis. It doesn't work like that. It is something that is acquired over time. Patients with high platelets and having ET will come to discuss diagnostic process may after, let's say, 15 or 20 years acquire fibrosis over time in the bone marrow.
And the doctor after seeing a patient after having that disease for 15 years says, Hmm, now you are anemic, and you have abnormal white cells in your bone marrow, and your spleen is enlarged. I need to do the bone marrow. Something is different. The bone marrow shows a lot of fibrosis. We talk about post-ET myelofibrosis. Patient has changed. The same disease, changing characteristics, new therapy is needed, new effort on the quality of life or even survival.
Now, we have criteria, ET versus PV versus myelofibrosis, and these criteria are made up usually of looking of course at the bone marrow, looking at the genetic component, meaning mutations, looking at the chromosomes that I mentioned before, looking at the spleen chemistry, looking at the blood count. All of this together would direct the doctor who puts this together to say, oh, hey, you have ET or you have a PV or you have myelofibrosis.
But, of course, now you know there is gray area. Sometimes we are a little bit insecure because either patients are in between really. Disease characteristics don't really fulfill all the criteria or partially that we made up. This is after all the expert opinion that we come together with to put these criteria in place. Or we don't have good samples. We talk many times about a dry tap. What is a dry tap in patients with myelofibrosis? There is too much scar tissue in the bone marrow, you can't really get a good sample from the bone marrow. So you have little difficulties when the samples are not either available or not tested properly. It is really occasionally, I would say, I hope occasionally is a good word, difficult to know, and occasionally you may need to repeat the testing even.
The Correct MPN diagnosis is a Team Effort
Just to sum up, Dr. Verstovsek, it sounds like there is still a lot of art in having an accurate diagnosis. It's the wisdom of the team coming together, helping you as a leader in the field, a specialist, come up with an accurate diagnosis.
Medicine is an art. There is a lot of science to it, but in this particular field of myeloproliferative neoplasms there is so much to connect together to make it the best we can, and you may call it art. It is science and art together.