Chronic eosinophilic leukemia associated with PDGFRA (PDGFRA-associated chronic eosinophilic leukemia) - Genes PDGFRA, and FIP1L1 chromosome 4
Chronic eosinophilic leukemia associated with PDGFRA, also known as chronic myelomonocytic leukemia, is a form of blood cell characterized by a high number of eosinophils in blood cancer. These cells help fight infection by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not explain the increase in the number of eosinophils in chronic eosinophilic leukemia associated with PDGFRA.
Another feature of the disease is organ damage due to excess eosinophils. Eosinophils release substances to help in the immune response, but the release of excessive amounts of these substances causes damage to one or more organs, most commonly the heart, skin, lungs or nervous system. The organ damage associated with eosinophils can result eosinophilic endomyocardial disease, skin rashes, cough, shortness of breath, edema of lower limbs, confusion, behavioral changes, or impaired movement or sensation. People with chronic eosinophilic leukemia associated with PDGFRA splenomegaly and may also have high levels of vitamin B12 and tryptase blood. Some people with associated chronic eosinophilic leukemia PDGFRA have an increased number of neutrophils or mast cells.
Occasionally, people with associated chronic eosinophilic leukemia PDGFRA develop other types of blood cell cancer such as acute myeloid leukemia, acute lymphoblastic leukemia or B cell or T - cell lymphoblastic lymphoma. Often chronic eosinophilic leukemia associated with PDGFRA grouped with a related process called hypereosinophilic syndrome. These two processes are very similar signs and symptoms; however, the cause of hypereosinophilic syndrome is unknown.
Chronic eosinophilic leukemia associated with PDGFRA develops as a result of mutations in the PDGFRA gene (receptor alpha platelet derived growth factor). This typically occurs due to genetic rearrangements that fuse of the PDGFRA gene from another gene. Rarely, point mutations in the PDGFRA gene found in those affected. The genetic rearrangements and point mutations affecting the PDGFRA gene are somatic mutations, acquired during the life of a person and that are present only in certain cells. The most common genetic abnormality responsible for chronic eosinophilic leukemia associated with PDGFRA, consists of a deletion of genetic material of chromosome 4, which includes a part of the gene and part of FIP1L1 PDGFRA gene (FIP1 like 1 -S. Cerevisiae-), resulting in the FIP1L1-PDGFRA fusion.
Gene PDGFRA (platelet derived growth factor receptor alpha), located on the long arm of chromosome 4 (4q12), encodes a protein called factor receptor alpha platelet derived growth (PDGFRA), which is part of the family tyrosine kinases (RTKs). The receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The PDGFRA protein is found in the cell membrane of certain types of cells where the protein platelet-derived growth factor, binds to it. This causes the activation of PDGFRA protein, which in turn activates the phosphorylation process. This process results in the activation of a number of proteins in multiple signaling pathways. Signaling pathways stimulated control PDGFRA protein play a role in many cellular processes such as growth, proliferation and cell survival. PDGFRA signaling protein is important for the development of many types of cells throughout the body.
The FIP1L1 (FIP1 like 1 -S. Cerevisiae-) gene, located on the long arm of chromosome 4 (4q12), encoding part of a protein complex called factor cleavage and polyadenylation specificity (CPSF). This protein complex plays an important role in mRNA processing.
The fusion gene FIP1L1-PDGFRA (and other PDGFRA fusion genes) encoding a fusion protein having the function of the normal protein PDGFRA. However, the fusion protein does not require binding a ligand to be activated. Similarly, point mutations in the gene PDGFRA can lead to PDGFRA protein is activated without ligand binding. As a result, the signaling pathways are constitutively active, which increases the proliferation and cell survival. When the gene mutation fusion FIP1L1-PDGFRA or point mutations in the gene PDGFRA occur in the precursors of blood cells, the growth of eosinophils and occasionally in other blood cells such as neutrophils and mast cells, bad controlled, resulting in disease. It is unclear why eosinophils are particularly affected by this genetic change.
Chronic eosinophilic leukemia associated with PDGFRA not inherited and occurs in people with no history of the disease in their families. Mutations that result PDGFRA fusion gene and point mutations are somatic mutations PDGFRA, meaning that occur during a person 's life and are found only in certain cells. Somatic mutations are not inherited. Males are more likely to develop chronic eosinophilic leukemia associated with PDGFRA women, since, for unknown reasons, PDGFRA fusion genes are most frequently in males.
Tests in IVAMI: in IVAMI perform detection of mutations associated with chronic eosinophilic leukemia associated with PDGFRA, by complete PCR amplification of the exons of the PDGFRA and FIP1L1 genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).