Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor updated 5/2021
Myeloproliferative neoplasms (MPN) are a related group of blood cancers. In these disorders, the bone marrow cells that produce blood cells develop and function abnormally. The three main types of MPN are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In addition to developing on its own, myelofibrosis may also develop as a result of ET or PMF.
PV and ET each result from the overproduction of certain types of blood cells. PMF involves scarring of the bone marrow and changes in blood cell production. The prognosis of these conditions varies greatly across people and by type of MPN. PV and ET both tend to be fairly slow-growing and may have only a modest effect on life expectancy. PMF tends to progress more rapidly, but the course of the disease can vary. Survival in PV is inferior to that of ET but superior to that of MF, with estimated medians of 14, 20, and 6 years. Recently treatment options have become available and treatment has been shown to provide improvement of symptoms.1,2 In rare cases, MPN can transform into a fast-growing type of blood cancer known as acute myeloid leukemia.
Myeloproliferative neoplasms are most common in older adults. Out of every 100,000 people in the United States, an estimated 44 to 57 people have PV, and a similar number have ET. Myelofibrosis is less common, affecting 4 to 6 people per 100,000.3
Like most cancers MPNs are caused by genetic mutations which can be inherited or acquired. Acquired mutations are caused by normal aging and exposure to carcinogens, such as radiation, certain chemicals, smoking, and some viruses and cannot be inherited by your children.
Inherited mutations are passed down from parents to children and are present in the DNA of your cells at birth. Inherited mutations are uncommon - MPNs are generally not considered to be inherited diseases
An important advance in our understanding of MPNs is the identification of specific genetic mutations that contribute to these conditions. In the case of myelofibrosis, this discovery has contributed to the development of new drugs to treat the condition.
Scientists have identified several acquired genetic mutations in blood stem cells that often play a role in the development of MPNs. The genetic mutations usually present in the three most common MPNs include the JAK2, CALR, and MPL gene markers.
- Polycythemia Vera ~ 95% of individuals with PV have a JAK2 gene mutation, CALR or MPL mutations may also be present.
- Essential Thrombocythemia may be associated with JAK2, CALR, or MPL genes. Approximately 60% involve a JAK2 gene mutation and 1/3 involve a MPL mutation. Primary
- Myelofibrosis Between 50 percent and 60 percent of MF have a JAK2 gene mutation. CALR and MPL gene mutations occur in 10%-30%
Mutations that disrupt the function of these genes can contribute to the uncontrolled growth of blood stem cells. Knowing which mutations are present in cancer cells helps doctors recommend the best treatment.
- JAK2 is a gene that makes a protein called Janus kinase 2, which sends signals in cells that promote cell growth.
- CALR is a gene that makes a protein called calreticulin, which helps control the amount of calcium stored in cells.
- MPL is a gene that makes a protein called the thrombopoietin receptor, which helps control the number of blood cells made in the bone marrow.
- C-kit, also called CD117 or stem cell factor receptor, is a protein that binds to a substance called stem cell factor (SCF), which causes certain types of blood cells to grow and can lead to cancer.
- Colony stimulating factor 3 receptor (CSF3R) is a gene that controls the growth and function of certain white blood cells.
Diagnosing a Myeloproliferative Neoplasm
Myeloproliferative neoplasms (MPNs) are blood cancers that involve the overproduction of one or more types of blood stem cells in the bone marrow. MPNs are diagnosed based on the results of a physical examination, blood tests, cytogenetic testing, and in some cases, a bone marrow biopsy.5
Cytogenetic testing is performed on the cells in order to determine if a cancer driving genetic mutation is present. Cytogenetic testing of chromosomes is done using fluorescent in situ hybridization (FISH) which used fluorescent molecules to highlight chromosomes and spot abnormalities and quantitative polymerase chain reaction (qPCR).5
Diagnostic Criteria for Specific MPN's
To learn more about the symptoms, diagnosis, and treatment of MPNs, select an option below.
Polycythemia vera: results from the overproduction of red blood cells. White blood cells and platelets may also be overproduced. The majority of individuals with PV will have a JAK2 mutation.
Essential thrombocythemia: results from the overproduction of platelets. Red blood cells and white blood cells may also be overproduced. Roughly 60 percent of individuals with ET have a JAK2 and 33% have an MPL mutation. CALR mutation may also be present.5
Myelofibrosis: results from the formation of scar tissue in the bone marrow, which interferes with the normal production of blood cells (red blood cells, white blood cells, and platelets).
Fifty to 60% of individuals with MF have a JAK 2 mutation and CLAR or MPL mutations are present in ~ 5-25%. Other genetic mutations may also contribute to MF.
Some individuals have no genetic mutations at all. These “Triple-Negative” MPNs occur in 12% of ET and 5% of individuals with MF. people with triple-negative MPNs may have less severe symptoms and slower disease.6
Chronic neutrophilic leukemia: This disorder causes you to have a surplus of neutrophils -- a certain type of white blood cell -- in your bloodstream.
Treatment Overview of Myeloproliferative Neoplasms
Treatment of a MPN is directed at the MPN causing genetic mutation and at the consequences of the MPN itself. MPN’s cause overproduction of blood stem cells and these excess blood cells enter the circulation and cause symptoms. Eventually the cells can overpopulate the bone marrow resulting in decreased production of functional blood cells resulting in anemia, low platelets and a risk of infection. Procedures to remove excess blood cells can temporarily improve MPN symptoms and lower the risk for serious complications.
Some individuals are at very low-risk from their disease and are not experiencing any symptoms. A watchful waiting or observation period rather than beginning treatment immediately may be recommended before initiating any treatment.
Excess red blood cells may be removed through the process of phlebotomy. Phlebotomy can temporarily improve symptoms and lowers the risk for blood clots. A process called apheresis can also be used to remove specific types of excess blood cells.
- Plateletpheresis is the removal of platelets and used to treat essential thrombocythemia.
- Leukapheresis is the removal of white blood cells.
Splenectomy An enlarged spleen (splenomegaly) is a common and uncomfortable symptom with some MPN's and some medications are effective at reducing the size of the spleen. in most people. For individuals that don't respond to medication surgical removal of the spleen may be necessary. Splenectomy can relieve pain and improve blood cell counts.
Patients with essential thrombocythemia and polycythemia vera are at increased risk of forming blood clots and doctors use medications to reduce the platelet count and lower the risk of blood clots.
- Agrylin (Anagrelide)
- Low-dose aspirin
Individuals at very high risk for blood clots may be prescribed the blood thinner Warfarin.
Conditions Related to Myeloproliferative Neoplasms
There are several health conditions that are significantly more common in people with MPNs than in the general population - these conditions can complicate treatment, add to the disease burden and are known to worsen fatigue in MPN’s.
Infections People with MPNs have a significantly higher risk for developing bacterial, viral, and fungal infections than people of similar ages who have not been diagnosed with MPN. Susceptibility to infections may be due to the MPN or its treatment.7
Blood and Bleeding Disorders Since MPNs cause overproduction of blood cells, and the blood cells tend to be abnormal and dysfunctional, it is not surprising that blood disorders are a common comorbidity. People living with an MPN are more likely to experience anemia, blood clots and bleeding problems. Blood clots can block arteries and cause life-threatening events such as stroke or pulmonary embolism. Symptoms of anemia include fatigue, weakness, pale skin, cold hands and feet, and shortness of breath. Anemia may be accompanied by feelings of pain, fullness, or pressure in the abdomen resulting from splenomegaly (enlarged spleen).
von Willebrand disease (VWD) is a bleeding disorder that can cause nosebleeds, excessive bleeding during dental and medical procedures, easy bruising, and heavy periods in women. In one study of 116 people with essential thrombocythemia (ET) and 57 people with polycythemia vera (PV), 55 percent of those with ET and 49 percent of those with PV developed acquired von Willebrand disease.13
Autoimmune Disorders People with MPNs may be predisposed to develop autoimmune (AI) disorders. Inflammation is a major aspect of autoimmunity and the direct cause of pain and tissue damage. In people with MPNs, AI conditions may worsen the symptom burden and even cause cancer cells to grow faster, contributing to disease progression.14 These are the autoimmune conditions associated with MPNs
- Crohn’s disease
- Aplastic anemia
- Polymyalgia rheumatica
- Reiter’s syndrome
- Giant cell arteritis
Secondary Cancers Individuals with an MPN have an increased risk for developing others cancers including
- Melanoma and Non-melanoma skin cancer
- Kidney, Brain, Endocrine, Pancreatic, Lung, and Head and neck cancers
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- Annucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59:171-191.
- Hultcrantz M, Kristinsson SY, Andersson TM, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:2995-3001.
- Mehta J, Wang H, Iqbal SU, Mesa R. Epidemiology of myeloproliferative neoplasms in the United States. Leukemia & lymphoma. 2013.
- Keohane C, Radia DH, Harrison CN. Treatment and management of myelofibrosis in the era of JAK inhibitors. Biologics : targets & therapy. 2013;7:189-198.
Landtblom AR, Andersson TML, Dickman PW, et al. Risk of infections in patients with myeloproliferative neoplasms — a population-based cohort study of 8363 patients [published online June 16, 2020]. Leukemia. doi: 10.1038/s41375-020-0909-7