Myeloproliferative Neoplasm

Myeloproliferative neoplasms are rare blood cancers that happen when your bone marrow makes too many blood cells—but with the right treatment, many people can manage these conditions and enjoy a near-normal lifespan.

Table of contents

• What Are Myeloproliferative Neoplasms?
• Understanding Your Bone Marrow and Blood Cells
• Types of Myeloproliferative Neoplasms
• Who Is Affected by These Conditions?
• What Causes Myeloproliferative Neoplasms?
• Symptoms of Myeloproliferative Neoplasms
• How Are Myeloproliferative Neoplasms Diagnosed?
• Treatment Options
• Outlook and Living with MPNs

MPN, myeloproliferative disorders, chronic myeloproliferative neoplasms, myeloproliferative diseases

• Bone marrow
• Blood cells
• Spleen
• Liver

What Are Myeloproliferative Neoplasms?

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers that occur when your bone marrow makes too many blood cells^[1]. The term myeloproliferative refers to the rapid growth of blood cells, while neoplasm means that this growth is abnormal and uncontrolled^[3]. These conditions are classified as blood cancers because the bone marrow produces blood cells in an uncontrolled way^[8].

MPNs develop very slowly, so people may have them for years before noticing any symptoms^[1]. The conditions are also called chronic myeloproliferative neoplasms or myeloproliferative disorders. The word chronic means that a condition is long-term^[1]. While these are serious conditions, many people with MPNs feel well and only need gentle treatment, as the disorders often develop slowly and progress slowly, or they can remain stable for a while^[8].

Understanding Your Bone Marrow and Blood Cells

To understand myeloproliferative neoplasms, it helps to know how your body normally makes blood cells. All blood cells start as stem cells in your bone marrow. Your bone marrow is soft, sponge-like tissue in the center of your bones that makes cells^[1].

Normally, the bone marrow makes blood stem cells that become mature blood cells over time^[2]. These stem cells can become myeloid stem cells or lymphoid stem cells. Lymphoid stem cells become white blood cells that help fight infection. Myeloid stem cells can develop into three types of mature blood cells^[2]:

• Red blood cells that carry oxygen throughout your body
• White blood cells that help fight infection and disease
• Platelets, which prevent excessive bleeding by helping blood clot

Like all cells, stem cells take instructions from genes that help dictate the cells’ form and function. Normally, your bone marrow makes stem cells that divide and multiply as needed. These stem cells follow directions from genes that help regulate cell development^[1].

In myeloproliferative neoplasms, acquired genetic mutations (changes) allow the blood stem cells in the bone marrow to create too many blood cells. When these genes mutate, they send new instructions to certain stem cells, telling the cells to keep on dividing and multiplying. Eventually, these stem cells become mature blood cells that pile up in your bone marrow or bloodstream, affecting blood flow. Blocked blood flow can cause serious medical conditions^[1].

Types of Myeloproliferative Neoplasms

The type of myeloproliferative neoplasm is based on whether too many red blood cells, white blood cells, or platelets are being made. Sometimes the body will make too many of more than one type of blood cell, but usually one type of blood cell is affected more than the others^[2].

The World Health Organization lists several types of MPNs^[3]:

• Chronic myeloid leukemia (CML) – characterized by the presence of the Philadelphia Chromosome, an abnormal chromosome^[3]
• Polycythemia vera (PV) – the most common myeloproliferative neoplasm that makes your bone marrow produce too many red blood cells^[1]
• Essential thrombocythemia (ET) – causes the bone marrow to produce too many platelets^[16]
• Primary myelofibrosis (PMF) – causes scarring of the bone marrow, preventing it from producing blood cells normally^[16]
• Chronic neutrophilic leukemia (CNL) – characterized by a mutation in the CSF3R gene and causes too many white blood cells to be produced^[3]
• Chronic eosinophilic leukemia (CEL) – affects a type of white blood cell and causes overproduction^[8]
• MPN, unclassifiable (MPN-U) – very rare myeloproliferative neoplasms that do not fall into the other categories^[8]

Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are the three most common types^[1]. These conditions are often associated with specific genetic mutations, particularly in the JAK2, CALR, TET2, and MPL genes^[3].

Who Is Affected by These Conditions?

About 20,000 Americans are diagnosed with myeloproliferative neoplasms each year^[16]. Myeloproliferative neoplasms affect multiple age groups, but they’re most common in people in their 50s, 60s or older^[1].

Your age and sex are the most significant predictors of how likely you are to have a myeloproliferative neoplasm. Polycythemia vera is generally more common in males, while essential thrombocythemia is more common in females. The remainder of the myeloproliferative neoplasms occur equally in both sexes^[1].

What Causes Myeloproliferative Neoplasms?

The exact cause of MPNs is not known. However, MPNs arise when precursor cells of the myeloid lineages in the bone marrow develop somatic mutations which cause them to grow abnormally^[3]. These genetic mutations usually arise during a person’s lifetime, rather than being passed along from one generation to the next. However, in rare instances, predisposition to genetic mutations may be inherited^[16].

Genetics is believed to play a central role in the development of MPNs, especially in developing complications such as blood clots and bleeding problems^[3]. A recurrent single change in the JAK2 gene has been identified in most patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis^[12]. Other genetic changes are associated with genes encoding calreticulin (CALR) and the thrombopoietin receptor (MPL)^[12].

In addition to genetic factors, exposure to high levels of ionizing radiation and toxins such as benzene has been associated with an increased risk of developing MPNs^[6]. MPNs share commonalities with chronic inflammatory diseases and, like those conditions, can be triggered by environmental exposures^[3].

Symptoms of Myeloproliferative Neoplasms

Many people with myeloproliferative neoplasms do not have any symptoms when their disease is first detected. You might be diagnosed after a routine blood test^[3][8].

The impact on your body varies based on the blood cell type affected. For example, one type of myeloproliferative neoplasm increases your risk of heart attack or stroke, while another type may cause anemia (a condition where you don’t have enough red blood cells)^[1].

If you do have symptoms, they might include^[8]:

• Tiredness or fatigue
• Bruising or unusual bleeding
• Getting more infections than usual
• Problems with your eyes, such as blurred vision
• Ringing in your ears
• Night sweats
• Itchy skin
• Weight loss
• Frequent headaches

If you do spot something unusual for you, tell your doctor. In most cases it won’t be cancer, but if it is, finding it early can make a difference^[8].

How Are Myeloproliferative Neoplasms Diagnosed?

Tests that examine the blood and bone marrow are used to diagnose myeloproliferative neoplasms^[2]. In addition to asking about your personal and family health history and doing a physical exam, your doctor may perform several tests and procedures.

Doctors use blood tests to diagnose myeloproliferative neoplasms. One key test is a complete blood count (CBC) with differential, which checks a sample of blood for^[2]:

• The number of red blood cells and platelets
• The number and type of white blood cells
• The amount of hemoglobin (the protein that carries oxygen) in the red blood cells
• The amount of hematocrit (whole blood that is made up of red blood cells)

The blood tests show the number of blood cells and can look for genetic mutations inside the blood cells^[8]. Direct sequencing of the patient’s DNA may be performed to identify specific genetic mutations^[3].

You might also have other tests, which might include^[8]:

• A bone marrow test
• An ultrasound of your abdomen
• Chest x-ray

Other tests depend on your symptoms and your general health. Before recommending treatments for MPNs, doctors assess an individual’s risk factors. These factors can increase a person’s likelihood of developing serious complications, such as blood clots, or increase the risk that their MPN will change into a more aggressive blood cancer^[15].

Treatment Options

There are treatments that ease symptoms and reduce the risk of a myeloproliferative neoplasm developing into a more serious disease^[1]. The aim of treatment is usually to control symptoms rather than cure the condition. In most cases, MPNs aren’t curable. However, new medications and treatment options have helped make MPNs more manageable as a long-term condition^[15].

Treatments are tailored to an individual’s specific MPN type, previous treatments, current blood counts, and unique risk factors^[15]. Treatment options might include^[8]:

• Venesection (also called phlebotomy) – a simple procedure for people with a high red blood cell count where around a pint of blood is removed, which will reduce the number of red cells in your blood
• Drugs to control the blood count – these might include weak forms of chemotherapy or drugs that target the immune system
• Bone marrow or stem cell transplant from a donor – this treatment aims to cure a myeloproliferative neoplasm and is the only curative treatment^[17]. However, this treatment is not suitable for everyone because it is an intensive treatment and it has many risks^[8]

For people with low-risk MPNs who don’t have symptoms, doctors may recommend a watch-and-wait approach rather than beginning treatment immediately. This approach, also referred to as watchful waiting or observation, involves closely monitoring a person’s condition for any signs or symptoms of progression^[15].

Myeloproliferative neoplasms sometimes become acute leukemia, in which too many abnormal white blood cells are made. In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia^[3]. There is no standard treatment approach for patients with progression from chronic-phase MPN to accelerated phase or blast phase, and these patients have a poor prognosis^[12].

Outlook and Living with MPNs

Because MPNs often progress slowly, many people with these conditions can enjoy a near-normal lifespan with the right treatment^[15]. MPNs are often associated with near-normal life expectancies when appropriately treated^[19].

Significant progress has been made in the last 20 years, allowing an operational cure of most patients with chronic myeloid leukemia, a type of myeloproliferative neoplasm previously associated with a much shorter life expectancy^[16].

Living with a myeloproliferative neoplasm can be challenging. Some strategies that can help include^[19]:

• Visiting a subspecialty center that focuses on MPNs
• Asking your care team questions about your treatment
• Managing stress through walks, meditation, or hobbies
• Joining support groups to connect with others experiencing similar things
• Speaking to a professional counselor
• Eating a healthy diet
• Getting regular exercise
• Allowing friends and family to help
• Learning about your disease from credible sources
• Continuing to live your life and do activities you enjoy

The MPN community is large and diverse. Many people living with an MPN enjoy meeting and sharing their experiences with others who can relate^[17].