Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers originating in the bone marrow. The name reflects the condition: “myelo” refers to bone marrow, “proliferative” describes rapid cell growth, and “neoplasm” indicates this growth is abnormal. In people with an MPN, the bone marrow overproduces red blood cells, white blood cells, or platelets. These conditions are chronic, developing slowly and persisting over a long period.
The World Health Organization (WHO) classifies MPNs as blood cancers due to the uncontrolled production of blood cells. This overproduction can lead to various health issues as the excess cells interfere with normal bodily functions. Because these diseases progress slowly, many individuals may not experience symptoms for years. Treatments are available to manage symptoms and reduce the risk of the disease progressing.
The Main Types of Myeloproliferative Neoplasms
The three main “classic” myeloproliferative neoplasms are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Each is distinguished by the specific type of blood cell that is overproduced. These conditions arise from issues within the bone marrow where blood cells originate.
Polycythemia vera (PV) is characterized by the excessive production of red blood cells. This overabundance thickens the blood and slows its flow. While red blood cells are most affected, PV can also lead to an increase in white blood cells and platelets. With careful management, many people diagnosed with PV can live for an average of 20 years after their diagnosis.
Essential thrombocythemia (ET) involves the overproduction of platelets. Platelets are small blood cells that help with clotting, and having too many can lead to an increased risk of blood clots. For many individuals with ET, life expectancy is normal, provided the condition is managed to prevent serious complications.
Primary myelofibrosis (PMF) is distinguished by the development of scar tissue, or fibrosis, within the bone marrow. This scarring disrupts the bone marrow’s ability to produce blood cells properly. As a result, the spleen and liver may begin to produce blood cells, leading to their enlargement. PMF can develop on its own or as a progression from PV or ET.
Chronic myeloid leukemia (CML) is also an MPN involving the overproduction of white blood cells called granulocytes. It is often categorized separately because it is associated with a specific genetic anomaly known as the Philadelphia chromosome. This distinction is significant as highly effective targeted therapies have been developed for CML, leading to a 90% five-year survival rate.
Underlying Causes and Genetic Factors
Myeloproliferative neoplasms develop from acquired genetic mutations in the hematopoietic stem cells of the bone marrow. These are not inherited conditions but rather changes that occur during a person’s lifetime. The mutations act like an “on” switch, signaling the bone marrow to produce an excessive number of blood cells.
The most frequently identified mutations are in the JAK2, CALR, and MPL genes. The discovery of the JAK2 gene’s association with MPNs in 2005, followed by the CALR gene in 2013, significantly improved the classification and diagnosis of these disorders. The JAK2 mutation is particularly common, found in a large percentage of patients with polycythemia vera and in about half of those with essential thrombocythemia and primary myelofibrosis. While the specific mutation can influence the disease, they all contribute to the overproduction of blood cells. Researchers are still investigating the triggers for these genetic mutations, but they are central to the development of MPNs.
Common Symptoms and Complications
Many symptoms of myeloproliferative neoplasms are shared across the different types. Common symptoms include persistent fatigue, night sweats, and itching, medically known as pruritus. An enlarged spleen, or splenomegaly, is also frequent and can cause a feeling of fullness or discomfort in the upper left abdomen.
The specific complications that can arise often depend on the type of MPN. For individuals with polycythemia vera and essential thrombocythemia, the increased blood thickness or high platelet count elevates the risk of blood clots, known as thrombosis. These clots can be life-threatening if they lead to a heart attack or stroke.
In primary myelofibrosis, the scarring of the bone marrow can lead to severe anemia from a lack of red blood cell production. There is also a risk for all MPNs to transform into a more aggressive blood cancer called acute myeloid leukemia (AML), which represents a serious progression of the disease.
The Diagnosis Process
The diagnostic process for an MPN begins when a routine complete blood count (CBC) reveals abnormally high levels of red blood cells, white blood cells, or platelets. These results can signal an underlying issue in the bone marrow.
If the CBC results are suspicious, a physician may recommend a bone marrow biopsy and aspiration. This procedure involves taking a small sample of bone and marrow from the hip bone for examination to assess marrow cellularity and check for abnormal cells or scarring.
To confirm the diagnosis, genetic testing is performed via a blood test. This screening looks for characteristic gene mutations, such as JAK2, CALR, and MPL. Identifying one of these mutations helps to confirm the diagnosis and can provide important information for determining the best course of treatment.
Treatment Approaches
Treatment for myeloproliferative neoplasms focuses on managing the condition as a chronic disease. For individuals at low risk without symptoms, a “watch and wait” approach may be adopted, involving regular monitoring.
For patients with polycythemia vera, a procedure called phlebotomy removes blood to reduce the red blood cell count and blood thickness. To lower the risk of blood clots in both PV and essential thrombocythemia, low-dose aspirin is prescribed. In some cases, cytoreductive therapies like hydroxyurea or interferon may be used to slow the production of blood cells.
More modern treatments include targeted therapies, such as JAK inhibitors like ruxolitinib. These medications block the activity of overactive proteins caused by the genetic mutations, helping to reduce symptoms and spleen size, particularly in primary myelofibrosis and polycythemia vera.
The only potential cure for MPNs is a stem cell transplant, which replaces the patient’s diseased bone marrow with healthy cells from a donor. This is a high-risk procedure reserved for younger, higher-risk patients due to its potential for serious complications. The choice of treatment depends on the specific type of MPN, the patient’s age and overall health, and their individual risk factors.