Also known as Myeloproliferative Leukaemia Gene (MPL), Thrombopoietin Gene (MPL) Mutation Detection; MPL W515L, MPL W515K Mutation. The MPL mutation test is used, along with other genetic testing to help diagnose bone marrow disorders that involve the overproduction of blood cells. These conditions are known as myeloproliferative neoplasms (MPNs).
What is being tested?
The MPL gene provides instructions for making the thrombpoetin receptor protein, which promotes cell growth and division and is especially important for controlling blood cell production from stem cells located within the bone marrow. This test looks for mutations in MPL that are associated with bone marrow disorders caused by an overproduction of blood cells.
Mutations in the MPL gene account for a small number of cases of essential thrombocytopaenia and primary myelofibrosis. These mutations lead to a protein that stimulates excess production of platelets (causing essential thrombocythaemia), and other cells to release collagen, a protein that normally provides structural support for the cells in the bone marrow but causes scar tissue formation in primary myelofibrosis
The primary MPL tests are MPL W515L, or MPL W515K, named for a mutation at a specific location in the MPL gene. These changes are acquired mutations (somatic) as opposed to an inherited mutation (germline) and results in the change of a single DNA nucleotide base pair. In MPL, this kind of mutation, called a point mutation, results in a thrombopoetin receptor protein that is constantly "on," leading to uncontrolled blood cell production.
How is it used?
The MPL mutation test may be used, along with other tests such as erythropoietin, to help diagnose bone marrow disorders that lead to overproduction of blood cells. These conditions are known as myeloproliferative neoplasms (MPNs).
The MPNs most commonly associated with MPL mutation are: polycythaemia vera (PV), in which the bone marrow makes too many red blood cells; essential thrombocythaemia (ET), in which there are too many platelet-producing cells in the bone marrow; and primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia, in which there are too many platelet-producing cells and cells that produce scar tissue in the bone marrow. The MPL mutation test is typically ordered as a follow-up test if a person has a significantly increased haemoglobin and/or platelet count and the medical practitioner suspects that the person may have an MPN.
When is it requested?
The MPL mutation test may be ordered along with other tests when a medical practitioner suspects that a person has a blood disorder known as a myeloproliferative neoplasm (MPN), especially polycythaemia vera (PV), essential thrombocythaemia (ET), or primary myelofibrosis (PMF). Many routine laboratory results such as a full blood count (FBC) reveal abnormal results associated with these MPNs, and someone may also have signs and symptoms that suggest an MPN.
Sometimes people with MPNs may have no symptoms or a few, relatively mild ones that may be present for years before being recognised as an MPN, often during a routine physical examination. However, if certain signs and symptoms appear, a health care provider may suspect that someone has one of these MPNs. They have many signs and symptoms in common, for example:
Polycythaemia vera (PV) may also be suspected when symptoms such as headaches, dizziness, visual distortion, itching and paraesthesia (abnormal skin sensation, such as tickling, tingling or numbness) appear. In PV, there are an excess number of red blood cells and the resulting blood thickening may lead to complications such as stomach ulcers, kidney stones, venous thrombosis, stroke and rarely to congestive heart failure. Since PV symptoms may be slow to appear, it is often discovered during routine blood tests.
Those with essential thrombocythaemia (ET) usually have no symptoms, but some may develop inappropriate blood clots (thrombosis) or bleeding (haemorrhage) because there are increased numbers of platelets produced that may not function properly. A blood clot could also cause a temporary interruption of blood flow to part of the brain (a transient ischemic attack) or stroke. Other symptoms from blood clots or excessive bleeding may include tingling in the hands and feet, headaches, dizziness, nosebleeds, and easy bruising.
Primary myelofibrosis (PMF) is a serious disorder that leads to bone marrow scarring and can eventually evolve into other, more serious forms of leukaemia. However, some people with PMF have no symptoms for years. People who do have symptoms may have those that are associated with severe anaemia, such as fatigue and weakness. A MPL mutation test may be done if routine laboratory tests suggest PMF.
What does the result mean?
If the MPL W515L or W515K mutation is detected and the person has other supporting clinical signs, then it is likely that the person has an MPN. Other testing, such as a bone marrow biopsy, may need to be performed to determine which MPN the person has and to evaluate its severity.
If the person is negative for MPL mutations, the person may still have an MPN. The person could have mutations in other genes such as JAK2. Mutation testing for both MPL and JAK2 are often ordered at the same time since both lead to the same symptoms.
Common questions
No. MPL mutation testing must be carried out by a laboratory that performs molecular testing. It is not offered by every laboratory and must often be sent to a reference laboratory.
Testing is not indicated unless someone has signs or symptoms that suggest an MPN. This is not a test that would be appropriate to use to screen the general population.
Yes, mutations in the Janus Kinase 2 (JAK2) gene, and the calreticulin gene (CAL-R) have been associated with ET and PMF. Genetic testing is also sometimes used to check for the presence or absence of a Philadelphia (Ph') chromosome or a bcr-abl translocation(see BCR-ABL) in a person suspected of having chronic myelogenous leukaemia.
Is MPL testing covered by Medicare?
Yes, a specialist doctor may order JAK2 and/or MPL mutation testing in the workup of suspected polycythaemia vera or essential thrombocythaemia. MBS item 73325
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