Get our free booklet, Myeloproliferative Neoplasms: In Detail
This booklet provides information about myeloproliferative neoplasms (myelofibrosis, polycythemia vera and essential thrombocythemia) and includes our Myeloproliferative Neoplasm Symptom Assessment Form to help you identify and keep track of your symptoms.
Download or order 50 free print copies today.
While certain signs and symptoms may indicate that a person has MF, a series of tests are needed to confirm the diagnosis. It is important to have an accurate diagnosis, as it helps the doctor to estimate how the disease will progress and determine the appropriate treatment. Some of these tests may be repeated both during and after treatment to evaluate the effectiveness of treatment.
Medical history and physical examination
Evaluation of an individual with suspected MF should start with a detailed medical history and a physical examination. The medical history should include information about the person’s:
- Cardiovascular risk factors, such as high blood pressure and diabetes
- Past illnesses and injuries
- Current and past medications, supplements, surgeries and blood transfusions
- History of thrombosis (the formation or presence of a blood clot inside a blood vessel) or hemorrhagic events (loss of blood from damaged blood vessels)
- Family medical history
- Current symptoms
After the medical history, the doctor will conduct a physical examination, during which the doctor may:
- Listen to the patient's heart and lungs
- Examine the patient's body for signs of disease
- Check different organs of the body
Tests your doctor may use to diagnose MF
Doctors may use several types of tests to diagnose MF. Open each section below to learn more.
There are several different blood tests used to diagnose MF.
Complete blood count (CBC) with differential
This test is used to measure the number red blood cells, white blood cells, and platelets in a sample of blood. It also measures the amount of the iron-rich protein that carries oxygen in red blood cells (hemoglobin) and the percentage of whole blood made up of red blood cells (hematocrit).
People with MF often have abnormally low levels of red blood cells. White blood cell counts are usually higher than normal, but in some patients, the white blood cell counts may be lower than normal. Platelet counts may be higher or lower than normal.
Peripheral blood smear
This is a procedure in which a sample of blood is viewed under a microscope. A pathologist examines the size, shape, and appearance of blood cells in the sample and checks for the presence of blast cells (immature blood cells). Blast cells are normally found in the bone marrow and are not typically found in the peripheral blood of healthy individuals. People with MF often have abnormal, teardrop-shaped red blood cells and immature blast cells in their blood.
Blood chemistry profile
This blood test measures the levels of certain substances released into the blood by organs and tissues in the body. These substances include electrolytes (such as sodium, potassium, and chloride), fats, proteins, glucose (blood sugar), uric acid, and enzymes. The test findings indicate how well a person’s kidneys, liver, and other organs are working. People with MF often have elevated serum levels of uric acid and LDH. During certain stages, MF causes many blood cells to die. Dying blood cells release LDH and uric acid.
Learn more about blood tests.
Your doctor tests your bone marrow to help confirm a diagnosis. Bone marrow testing involves two steps, usually performed at the same time in a doctor's office or a hospital.
They are:
- A bone marrow aspiration to remove a liquid marrow sample
- A bone marrow biopsy to remove a small amount of bone filled with marrow
A pathologist studies the samples under the microscope and examines the chromosomes inside the cells. Patients with MF typically have an increased number of megakaryocytes (platelet-forming cells) that are unusual in size and shape and fibrosis in the bone marrow. In some patients who have MF, it is not possible to obtain a liquid sample during a bone marrow aspiration due to scarring in the bone marrow. The scarring will cause
Learn more about bone marrow tests.
View the interactive 3D model to help you visualize and better understand the procedure. Click or tap the "Interact in 3D" button to begin.
These laboratory tests examine the cancer cells from the blood, bone marrow or other tissues to check for certain genes, proteins or other molecules to provide information about a person’s cancer. Each person’s cancer has a unique pattern of biomarkers. Biomarker testing may also be used to help plan treatment, find out how well treatment is working or predict whether cancer will come back or spread to other parts of the body
Cytogenetic analysis (Karyotyping)
This test is used to look for abnormal changes in the chromosomes of the cancer cells. Normal human cells contain 23 pairs of chromosomes, for a total of 46 chromosomes. Each pair of chromosomes is a certain size, shape, and structure. In some cases of MF, the chromosomes of the cancer cells have abnormal changes that can be seen under a microscope, such as extra or missing chromosomes, or broken or rearranged chromosomes. Some patients with MF have a “complex karyotype,” which is when there are three or more unrelated abnormalities in the chromosomes.
Polymerase chain reaction (PCR)
This is a very sensitive test used to detect and measure specific genetic mutations that are too small to be seen with a microscope. PCR testing essentially amplifies (increases) small amounts of specific pieces of DNA so that they are easier to detect and measure in a cell sample. It looks for the presence or absence of specific gene mutations. PCR testing can be done with blood or bone marrow samples.
Next-generation sequencing (NGS) Next-generation sequencing, also called “molecular testing” or “genomic testing,” refers to a number of different laboratory tests that examine the exact sequence (order) of DNA or RNA. This makes it possible to identify a variety of genetic changes in a patient’s cancer cells. These changes are important in guiding risk assessment and prognosis and may also inform treatment decisions for targeted therapy specific to the particular change in the genetic sequence of the cancer cell. The information these tests provide can help doctors to determine which patients are at high risk and may need more intensive treatment or may benefit from treatment with new therapies.
Next-generation sequencing may be done when the cancer is first diagnosed and is also used after treatment for evaluating measurable residual disease (MRD). It can find one cancer cell among one million normal bone marrow cells.
Approximately 90% of patients with MF have a mutation of the JAK2, MPL, or CALR gene.
The approximate frequencies of these mutations are:
- JAK2 mutation: 60 percent
- CALR mutation: 20 percent to 30 percent
- MPL mutation: 7 percent to 10 percent
About 10 percent of MF patients do not have a JAK2, MPL, or CALR gene mutation. In these cases, the disease is referred to as “triple-negative” MF, and it is associated with a worse prognosis (outcome).
Over the last several years, numerous other gene mutations have been identified in patients with primary MF including the genes called CBL, LNK/ SH2B3, ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, DNM3TA, SF3B1, SRSF2, and U2AF1. These mutations may occur in addition to JAK2, CALR or MPL mutations; a person with MF may have several of these mutations at the same time. Scientists are investigating the role that these and other mutations may have in the onset and progression of MF
Learn more about blood tests.
Although HLA typing is not used to daignose MF, HLA typing should be performed for patients who are candidates for an allogeneic stem cell transplantation. HLAs play an important role in the body’s immune response to foreign substances by helping the body distinguish its own cells from foreign cells. HLA matching is done prior to a donor stem cell transplantation to find out if tissues between the donor and the person receiving the transplant match.
Criteria for diagnosing MF
According to the 2016 World Health Organization criteria for diagnosing primary MF, a diagnosis requires all three major criteria plus at least one minor criteria from the list below:
Major criteria
- Proliferation of abnormal megakaryocytes accompanied by fibrosis in the bone marrow, grade <2
- Exclusion of other diseases defined by World Health Organization criteria, such as essential thrombocythemia, polycythemia vera, BCR-ABL1+ chronic myeloid leukemia, myelodysplastic syndromes, or other myeloid neoplasms
- Presence of JAK2, CALR, or MPL mutation or another clonal marker (gene mutation) such as genes ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1, or the absence of reactive myelofibrosis
Minor criteria
Presence of at least one of the following, confirmed in two consecutive tests:
- Anemia not caused by another condition
- White blood cell count greater than or equal to 11 × 109/L
- Palpable enlarged spleen
- Lactate dehydrogenase (LDH) level above upper normal limits
- Presence of immature blood cells in the peripheral blood (called "leukoerythroblastosis")
Get free, one-on-one support
Call, email, or chat with a member of our highly trained support team.
Blood Cancer United resources
Find free, specialized guidance and information for every type of blood cancer, request financial support, find emotional support, and connect with other members of the blood cancer community.
