Hypereosinophilic syndrome - Genetics Home Reference
Hypereosinophilic syndrome
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Reviewed February 2012
What is hypereosinophilic syndrome?
Hypereosinophilic syndrome is characterized by an elevated number of eosinophils (hypereosinophilia) in the blood. Eosinophils are a type of white blood cell involved in immune system function. These cells are increased in response to infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, there are no signs of infection or allergy to account for the increased number of eosinophils in people with this condition.
Another characteristic feature of hypereosinophilic syndrome is organ damage caused by the excess eosinophils. Eosinophils release substances to aid in the immune response, but the release of increased amounts of these substances causes damage to one or more organs, most commonly the skin, heart, lungs, or nervous system. Affected individuals may have skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, or impaired movement or sensations.
Some people with hypereosinophilic syndrome have an increased number of other white blood cells, such as immune cells called neutrophils or mast cells. In addition, people with hypereosinophilic syndrome may have an increased risk of developing a blood cell cancer such as acute myeloid leukemia or T-cell lymphoma.
Another characteristic feature of hypereosinophilic syndrome is organ damage caused by the excess eosinophils. Eosinophils release substances to aid in the immune response, but the release of increased amounts of these substances causes damage to one or more organs, most commonly the skin, heart, lungs, or nervous system. Affected individuals may have skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, or impaired movement or sensations.
Some people with hypereosinophilic syndrome have an increased number of other white blood cells, such as immune cells called neutrophils or mast cells. In addition, people with hypereosinophilic syndrome may have an increased risk of developing a blood cell cancer such as acute myeloid leukemia or T-cell lymphoma.
How common is hypereosinophilic syndrome?
Hypereosinophilic syndrome is a rare condition; however, the exact prevalence is unknown.
What are the genetic changes related to hypereosinophilic syndrome?
The PDGFRA gene is involved in 15 to 20 percent of hypereosinophilic syndrome cases. Hypereosinophilic syndrome can occur as a result of genetic rearrangements that cause the fusion of the PDGFRA gene with another gene. These mutations are somatic mutations, which are mutations acquired during a person's lifetime that are present only in certain cells.
The most common PDGFRA-associated genetic abnormality in hypereosinophilic syndrome results from a deletion of genetic material from chromosome 4, which brings together the PDGFRA gene and the FIP1L1 gene, creating the FIP1L1-PDGFRA fusion gene. Hypereosinophilic syndrome caused by a PDGFRA fusion gene is also known as chronic eosinophilic leukemia or PDGFRA-associated myeloproliferative neoplasm.
The FIP1L1 gene provides instructions for a protein that plays a role in forming the genetic blueprints for making proteins (messenger RNA or mRNA).
The PDGFRA gene provides instructions for making a receptor protein that is found in the cell membrane of certain cell types. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When the ligand attaches (binds), the PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and cell survival.
The FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) provides instructions for making a fusion protein that has the function of the normal PDGFRA protein. However, the fusion protein does not require ligand binding to be activated. As a result, the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When the FIP1L1-PDGFRA mutation occurs in blood cell precursors, eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) grow uncontrollably, leading to hypereosinophilic syndrome. It is unclear why eosinophils are preferentially affected by this genetic change.
Some cases of hypereosinophilic syndrome seem to be caused by elevated numbers of immune cells called T cells. These cases are sometimes referred to as the lymphoid variant of hypereosinophilic syndrome because T cells are a type of lymphoid cell. T cells release a growth factor called interleukin-5 (IL-5), which stimulates eosinophils to grow and divide. In this form of hypereosinophilic syndrome, the T cells release excess levels of IL-5, leading to hypereosinophilia. However, the reason for the elevated numbers of T cells is unknown.
Most people with hypereosinophilic syndrome do not have an identified genetic mutation. The cause of the condition in these individuals is unknown.
Read more about the FIP1L1 and PDGFRA genes and chromosome 4
The most common PDGFRA-associated genetic abnormality in hypereosinophilic syndrome results from a deletion of genetic material from chromosome 4, which brings together the PDGFRA gene and the FIP1L1 gene, creating the FIP1L1-PDGFRA fusion gene. Hypereosinophilic syndrome caused by a PDGFRA fusion gene is also known as chronic eosinophilic leukemia or PDGFRA-associated myeloproliferative neoplasm.
The FIP1L1 gene provides instructions for a protein that plays a role in forming the genetic blueprints for making proteins (messenger RNA or mRNA).
The PDGFRA gene provides instructions for making a receptor protein that is found in the cell membrane of certain cell types. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When the ligand attaches (binds), the PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and cell survival.
The FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) provides instructions for making a fusion protein that has the function of the normal PDGFRA protein. However, the fusion protein does not require ligand binding to be activated. As a result, the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When the FIP1L1-PDGFRA mutation occurs in blood cell precursors, eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) grow uncontrollably, leading to hypereosinophilic syndrome. It is unclear why eosinophils are preferentially affected by this genetic change.
Some cases of hypereosinophilic syndrome seem to be caused by elevated numbers of immune cells called T cells. These cases are sometimes referred to as the lymphoid variant of hypereosinophilic syndrome because T cells are a type of lymphoid cell. T cells release a growth factor called interleukin-5 (IL-5), which stimulates eosinophils to grow and divide. In this form of hypereosinophilic syndrome, the T cells release excess levels of IL-5, leading to hypereosinophilia. However, the reason for the elevated numbers of T cells is unknown.
Most people with hypereosinophilic syndrome do not have an identified genetic mutation. The cause of the condition in these individuals is unknown.
Read more about the FIP1L1 and PDGFRA genes and chromosome 4
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