In order to understand myelodysplastic/myeloproliferative neoplasms (MDS/MPN) disease overlap, it’s important to first differentiate between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). MDS represents a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. Cells look abnormal under the microscope and those with this disease tend to have low blood cell counts. Some of the symptoms of MDS include infection, anemia, bleeding, and bruising. These problems are largely the result of abnormal blood cell numbers or function. Some patients diagnosed with MDS will eventually develop an acute leukemia. The risk of this happening is not the same for all patients with MDS. There are several important features of MDS that help physicians predict whether a patient’s MDS is more or less likely to transform into an acute leukemia, however, these tools are imperfect.

Myeloproliferative neoplasms (MPNs) are a group of diseases that affect normal blood cell production in the bone marrow. Generally, MPNs are characterized by an overproduction of blood cells, also known as proliferation. Bone marrow is the factory for virtually all blood cells and when the body needs more blood cells, the bone marrow is normally able to ramp up production. For instance, when a healthy person has an infection, the bone marrow can produce more white blood cells to help fight against the infection. When the infection is over, the bone marrow returns to normal. However, in someone with MPN, the bone marrow is producing too many blood cells even when they are not needed. The results in an abnormally high number of blood cells that accumulate in the bone marrow and in the circulating blood. This can increase the risk of blood clots or, sometimes, can increase the risk of bleeding.

The overproduction of blood cells is also commonly linked to blood cells being produced in abnormal places, most typically in the spleen. This can cause the spleen to enlarge. Patients with MPNs also often experience symptoms like fatigue, insomnia, mood disorders and shortness of breath that are not directly tied to blood cell counts. Although increased numbers of at least one blood cell type is very common for patients with MPNs, some MPNs also cause abnormally low blood counts. This is sometimes the result of bone marrow scarring, or fibrosis, that can develop in patients with certain types of MPNs. Low blood counts can also be the result of abnormal blood cell production due to particular mutations found in the MPN cells. Much like MDS, some cases of MPNs have the potential to progress to leukemia. 

Myelodysplastic diseases/myeloproliferative neoplasms (MDS/MPN) represent a distinct category of myeloid disorders that possess both dysplastic and proliferative features. These disorders are not properly classified as either MDS or MPN because they have some features of both MDS and MPNs. The MDS/MPN category includes three major myeloid disorders: chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myeloid leukemia (aCML). Another category that myeloid diseases sometimes fall into is known as myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC), which is when the disease shows features of both MDS and MPN but does not meet the criteria for any of the three major MDS/MPN categories. The signs and symptoms for those with MDS/MPN overlap vary from person to person, but can include any of the following, anemia, high platelet count, fatigue, night sweats, shortness of breath, dizziness and enlargement of spleen. As is true with MDS and some MPNs, MDS/MPNs can transform to acute leukemias.

Currently there is a lack of published registry data on the precise incidence of the various subtypes, though there is a perception that the relative incidence of MDS/MPN is relatively low.

The incidence of MDS/MPN varies widely, ranging from approximately 3 per 100,000 individuals older than 60 years annually for CMML to as few as 0.13 per 100,000 children from birth to 14 years annually for JMML, according to the National Cancer Institute.

There has been quite a bit of progress understanding the molecular origins of MDS/MPN myeloid neoplasms. Although there are no firm guidelines on how and when to treat MDS/MPN, the decision on which treatment to use is often based upon the symptoms experienced by patients and the perceived risk of transformation to a leukemia. Sometimes, bone marrow transplant is considered the best way to treat the disease. NewYork-Presbyterian Hospital/Weill Cornell Medicine offers one of the best Bone Marrow and Stem Cell Transplant (BMT) programs in the United States and around the world.

Additional potential treatments for the disease include cytoreductive agents (hydrea, lenalidomide) and medications to lower blood count such as DNA hypomethylating agents (decitabine/Dacogen, azacitiding/Vidaza). In order to continue advancing treatment options for this population, clinical trials should always be considered. Without the voluntary participation of countless patients in many studies, new effective therapies would be impossible to develop. Learn more about trials available through our NewYork-Presbyterian and Weill Cornell Medicine Joint Clinical Trials Office (JCTO).


Richard T. Silver MD Myeloproliferative Neoplasms Center 525 East 70th St., Starr Pavillion, 3rd Floor New York, NY 10021