PDGFRB-associated chronic eosinophilic leukemia - Genetics Home Reference
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PDGFRB-associated chronic eosinophilic leukemia
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Reviewed February 2013
What is PDGFRB-associated chronic eosinophilic leukemia?
PDGFRB-associated chronic eosinophilic leukemia is a type of cancer of blood-forming cells. It is characterized by an elevated number of white blood cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRB-associated chronic eosinophilic leukemia. Some people with this condition have an increased number of other types of white blood cells, such as neutrophils or mast cells, in addition to eosinophils. People with this condition can have an enlarged spleen (splenomegaly) or enlarged liver (hepatomegaly). Some affected individuals develop skin rashes, likely as a result of an abnormal immune response due to the increased number of eosinophils.
How common is PDGFRB-associated chronic eosinophilic leukemia?
The exact prevalence of PDGFRB-associated chronic eosinophilic leukemia is unknown. For unknown reasons, males are up to nine times more likely than females to develop PDGFRB-associated chronic eosinophilic leukemia.
What are the genetic changes related to PDGFRB-associated chronic eosinophilic leukemia?
PDGFRB-associated chronic eosinophilic leukemia is caused by genetic rearrangements that join part of the PDGFRB gene with part of another gene. At least 20 genes have been found that fuse with the PDGFRB gene to cause PDGFRB-associated chronic eosinophilic leukemia. The most common genetic abnormality in this condition results from a rearrangement (translocation) of genetic material that brings part of the PDGFRB gene on chromosome 5 together with part of the ETV6 gene on chromosome 12, creating the ETV6-PDGFRB fusion gene.
The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes, including cell growth and division (proliferation). The ETV6 gene provides instructions for making a protein that turns off (represses) gene activity. This protein is important in development before birth and in regulating blood cell formation. The protein produced from the ETV6-PDGFRB fusion gene, called ETV6/PDGFRβ, functions differently than the proteins normally produced from the individual genes. Like the normal PDGFRβ protein, the ETV6/PDGFRβ fusion protein turns on signaling pathways. However, the fusion protein does not need to be turned on to be active, so the signaling pathways are constantly turned on (constitutively activated). The fusion protein is unable to repress gene activity regulated by the normal ETV6 protein, so gene activity is increased. The constitutively active signaling pathways and abnormal gene activity increase the proliferation and survival of cells.
When the ETV6-PDGFRB fusion gene mutation occurs in cells that develop into blood cells, the growth of eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRB-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.
Read more about the ETV6 and PDGFRB genes, chromosome 5, and chromosome 12.
The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes, including cell growth and division (proliferation). The ETV6 gene provides instructions for making a protein that turns off (represses) gene activity. This protein is important in development before birth and in regulating blood cell formation. The protein produced from the ETV6-PDGFRB fusion gene, called ETV6/PDGFRβ, functions differently than the proteins normally produced from the individual genes. Like the normal PDGFRβ protein, the ETV6/PDGFRβ fusion protein turns on signaling pathways. However, the fusion protein does not need to be turned on to be active, so the signaling pathways are constantly turned on (constitutively activated). The fusion protein is unable to repress gene activity regulated by the normal ETV6 protein, so gene activity is increased. The constitutively active signaling pathways and abnormal gene activity increase the proliferation and survival of cells.
When the ETV6-PDGFRB fusion gene mutation occurs in cells that develop into blood cells, the growth of eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRB-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.
Read more about the ETV6 and PDGFRB genes, chromosome 5, and chromosome 12.
Can PDGFRB-associated chronic eosinophilic leukemia be inherited?
PDGFRB-associated chronic eosinophilic leukemia is not inherited and occurs in people with no history of the condition in their families. Chromosomal rearrangements that lead to a PDGFRB fusion gene are somatic mutations, which are mutations acquired during a person's lifetime and present only in certain cells. The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population).
Where can I find information about diagnosis or management of PDGFRB-associated chronic eosinophilic leukemia?
These resources address the diagnosis or management of PDGFRB-associated chronic eosinophilic leukemia and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
- Cancer.Net: Leukemia--Eosinophilic:
Treatment - MedlinePlus Encyclopedia: Eosinophil
Count--Absolute - Seattle Cancer Care Alliance:
Hypereosinophilia
General information about the diagnosis and management of genetic conditions is available in the Handbook.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about PDGFRB-associated chronic eosinophilic leukemia?
You may find the following resources about PDGFRB-associated chronic eosinophilic leukemia helpful. These materials are written for the general public.
- MedlinePlus - Health information (2 links)
- Additional NIH Resources - National Institutes of Health
- Educational resources - Information pages (5 links)
- Patient support - For patients and families (4 links)
ClinicalTrials.gov - Linking patients to medical researchPubMed - Recent literature
What other names do people use for PDGFRB-associated chronic eosinophilic leukemia?
- atypical Philadelphia-negative chronic myeloid leukemia
- chronic myelomonocytic leukemia
- chronic myeloproliferative disorder with eosinophilia
- clonal eosinophilia with chronic myeloproliferative disorder
- primary eosinophilia with chronic myeloproliferative disorder
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.
What if I still have specific questions about PDGFRB-associated chronic eosinophilic leukemia?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
- What does it mean if a disorder seems to run in my family?
- What is a chromosome?
- Can changes in the number of chromosomes affect health and development?
- Are chromosomal disorders inherited?
What glossary definitions help with understanding PDGFRB-associated chronic eosinophilic leukemia?
atypical ;cancer ;cell ;chromosome ;chronic ;chronic myelomonocytic leukemia ;enlarged spleen ;eosinophils ;gene ;immune response ;infection ;inflammation ;juvenile ;juvenile myelomonocytic leukemia ;leukemia ;mast cells ;mutation ;myeloid ;neutrophils ;population ;prevalence ;proliferation ;protein ;rearrangement ;somatic mutation ;splenomegaly ;syndrome ;translocation ;white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (10 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.
Reviewed: February 2013
Published: February 11, 2013
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