FIP1L1-PDGFRA

This test is used to detect the genetic mutation FIP1L1-PDGFRA. FIP1L1-PDGFRA is an abnormal gene sequence that causes excessive growth of eosinophils, a type of white blood cell.

Eosinophils are part of the body's immune response and can be elevated in the blood with different diseases and conditions. Some common examples are allergic responses and parasitic infections. A complete blood count (CBC) is a test that may show increased numbers of eosinophils in the blood (hypereosinophilia) with these conditions.

The FIP1L1-PDGFRA gene sequence is a rare cause of increased eosinophils. Testing for the mutation may be used to help determine the cause of a persistently elevated number of eosinophils, as determined by a CBC, after other tests have ruled out more common secondary causes. These other tests may include, for example, allergy blood tests or stool tests for parasites. (See Common Questions for more on these.)

FIP1L1-PDGFRA testing may be used to:

• Help diagnose the cause of hypereosinophilia (HE) and hypereosinophilic syndrome (HES), a type of bone marrow disorder
• Help determine HE/HES prognosis and responsiveness to therapy with a tyrosine kinase inhibitor (TKI); people with FIP1L1-PDGFRA respond well to treatment with a TKI called imatinib.

See Common Questions for more details on test methods.

Tests for FIP1L1-PDGFRA may be performed along with other genetic tests for less common mutations related to eosinophilia. It may also be performed along with:

• Chromosme analysis – to detect other genetic abnormalities that may be the cause of HE/HES, such as PDGFRB or FGFR1 rearrangement
• BCR-ABL1 – if chronic myelogenous leukemia (CML) is suspected and thus needs to be ruled out
• KIT mutation – to rule out mutation in the KIT gene; people with KIT D816 mutation (mastocytosis) do not respond to imatinib treatment.
• Interleukin-5 – may be tested because, if elevated, it suggests clonal T-cell disease when found with HES
• Immunoglobulin E (IgE) level – people with elevated IgE levels may have a lower risk of developing hypereosinophilic syndrome-associated cardiovascular disease and may respond well to steroid therapy.
• An initial evaluation of HES may include cardiac tests to look for evidence of organ damage from the condition and a troponin test to make sure imatinib won't cause cardiac shock.

FIP1L1-PDGFRA testing is ordered when CBCs indicate that someone has persistently elevated numbers of eosinophils and other causes like allergies, asthma, parasitic infections, adrenal insufficiency, and lymphoma have been ruled out.

Testing may be ordered after an abnormal eosinophil count when HES is suspected due to a person's signs and symptoms. HES and leukemias (either acute or chronic) may have similar presentations, but sometimes there are no early symptoms and the conditions are found only through a routine CBC.

Examples of common HES signs and symptoms include:

• Fever
• Fatigue
• Cough, wheezing, shortness of breath
• Swelling under the skin around the eyes and lips, in the throat, or on the hands and feet
• Swollen lymph nodes or organs
• Muscle pain
• Itching, rash or blistering of the skin
• Diarrhea

The result of the test may be reported as "positive" (the gene sequence is present) or as "negative" (the gene sequence is not present).

If a person has abnormally high numbers of eosinophils and tests positive for the FIP1L1-PDGFRA fusion gene, then the fusion gene is confirmed as the underlying cause of that person's hypereosinophilia (HE) or hypereosinophilic syndrome (HES).

Note that HE/HES with FIP1L1-PDGFRA may be diagnosed as acute or chronic leukemia, a myeloproliferative or myelodysplastic disorder, or even systemic mastocytosis, based on the World Health Organization's 2008 diagnostic guidelines. Regardless the diagnosis, individuals with the FIP1L1-PDGFRA fusion gene respond very well to treatment with the tyrosine kinase inhibitor imatinib.

If a person tests negative for FIP1L1-PDGFRA, depending on other test results, the person may have another type of myeloproliferative or myelodysplastic neoplasm or may be diagnosed with HES without a specific cause (idiopathic). FIP1L1-PDGFRA-negative cases of HES do not respond as well to imatinib except for rare cases with PDGFRB rearrangement (see below).

Sometimes people develop resistance to imatinib even though the tyrosine kinase inhibitor is usually very effective for treating people with the FIP1L1-PDGFRA fusion gene at low doses. For the rare individuals whose HES is resistant to imatinib, stem cell transplants have reversed the organ dysfunction caused by hypereosinophilia. However, health practitioners have limited experience with this treatment, so it is not used routinely. Chemotherapy has also been used with some success for people with the fusion gene who don't respond to treatment with imatinib. Some individuals with the fusion gene are also treated with corticosteroids to lower their eosinophil count and help control organ damage.

People with FIP1L1-PDGFRA may also manifest as acute myeloid or lymphoblastic leukemia, though that is rare. FIP1L1-PDGRA has also been found infrequently in other leukemias and successfully treated with imatinib.

Unlike some other genetic abnormalities, FIP1L1-PDGFRA related change is very subtle and thus cannot be detected with routine karyotyping, which involves looking at chromosomes under a microscope.

No. The chromosome deletion that leads to the FIP1L1-PDGFRA fusion is what is known as somatic. It is a mutation acquired during a person's lifetime and cannot be inherited.