Is myelodysplastic syndrome a myeloproliferative neoplasm? What are myeloproliferative neoplasms? Can an myeloproliferative neoplasms also turn into acute myeloid leukemia?

Is MDS a myeloproliferative neoplasm (MPN)?

So what I would say MPNs are, you have more normal looking cells. There are just more of them. So a good example is polycythemia vera, which is an MPN. What you have is you have extra blood cells, so your red blood cell count is high, but those red blood cells look pretty normal. So you just have more of them. With MDS, typically what you see is you see all blood counts are lower. So they're not higher. They're lower. So that's one of the things.

So the way we think about MDS is that there's some problem in the bone marrow where you're making cells, but they're just not maturing properly and they're not getting out there into the blood. That's why you have low blood counts. With MPN, you're just making excessive ones, they're all doing their normal maturation, but you're just getting more of them. And it could be that the white blood cells go up in that you have something called CML or chronic myeloid leukemia. It could be that you have polycythemia vera, where the red blood cells are high, or you could have something called essential thrombocytopenia, where your platelets are high.

But they are with MPNs just like MDS. One of the fears is that those things now become AML, like those can become AML just like MDS. There are some diseases where there's an overlap of the two. So there's one weird disease called chronic myelomonocytic leukemia, CMML, and that sometimes looks like an MPN and sometimes it looks like MDS. And we sort of treat them a little bit differently depending on how they kind of look. But they're really the same disease.

So the definitions are not super precise, but the way I think about it is high blood counts = MPN, but the way I think about it is high blood counts = MPN. Because it's proliferative. Low blood counts = MDS, they're dysplastic. They're just not doing what they should do, maturation-wise, well. So that's why counts are low. So it's high counts versus low counts. That's the easiest way to think of the difference between an MPN and MDS.

So myeloproliferative is an MPN, but it is a disease where you quickly start to develop low blood counts. So you might have higher blood counts in the beginning, but because the bone marrow becomes scarred, it's not as good at making blood. And so then at that point in time, you start to have low blood counts. And so one other thing with MPN is frequently you can have a big spleen in MPNs, and that's pretty rare to have in MDS. And having a big spleen is a problem because it takes up a lot of room in your abdomen. And so you can start to lose weight. You can get very fatigued with the big spleen, so it causes a lot more symptoms if you have splenomegaly.

So that's one of the major ways that MPNs cause symptoms that MDS does not. MDS, you might be tired because you have anemia and pains, you might be tired, you have normal, you don't have anemia because of this huge spleen. And that's just sucking all the energy from you. That could make you tired. So it's different. It might be different ways of getting to the same place. While we try to define these diseases like MDS or MPNs, that's really not how nature works. And things are in a continuum and really just putting up these barriers between these different diseases that are kind of artificial and arbitrary.

So there are patients who have a shared biology that have both features of myeloproliferative neoplasms, such as a big spleen, such as constitutional symptoms, fevers, night sweats and weight loss, but also have features of myelodysplastic syndrome. And specifically, there's four of these different MDS/MPN overlap syndromes. And these different diseases have these shared features where they have both clinical and pathologic features of MDS and clinical and pathologic features of MPNs.

But they don't really belong to either group, MDS or MPN, and they have very unique features which makes treating them very challenging. They've also been traditionally ignored in terms of clinical trials, where they'll be excluded from trials for MPNs and excluded from trials for MDS. And so we don't have as much information about the optimal treatment for these patients.

And so a lot of effort now is going into trying to understand what the unique biology of these patients is, what their risks are, how to predict what their outcomes are going to be, and then how we can learn from what the treatment paradigms are from MDS and MPNs and combine that knowledge to really see how we can treat these patients more effectively.

It's a tough field, but it's also one that is becoming increasingly recognized. And because it's becoming increasingly recognized, I'm hopeful that there is going to be more research and more understanding about how to adequately treat these patients instead of just treating them like they have MPN or treating them like they have MDS. How to tailor treatment options and study this in a way that is specific for this group of patients.

Can an MPN turn into AML?

It does, and so that's the biggest thing about MPNs. That has the highest chance, I think, of getting to AML. CML can go to AML as well. But CML is the place where we have things like Gleevec and other tyrosine kinase inhibitors that have really revolutionized the way we take care of those patients. There's some data out there that suggests that if you are well-controlled on a TKI, you have CML, you probably live as long as anybody else without CML. Just maintaining that control with that.

So that has been like the poster child of how science advances clinical care and how that clinical care really makes a difference now for patients.