Platelet-derived growth factor receptor A, also termed CD140a, is a
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
located on the surface of a wide range of cell types. The protein is encoded in the human by the ''PDGFRA''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. This receptor binds to certain
isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
s of
platelet-derived growth factor
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing bloo ...
s (PDGFs) and thereby becomes active in stimulating
cell signaling
In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
pathways that elicit responses such as
cellular growth and
differentiation. The receptor is critical for the
embryonic development
In developmental biology, animal embryonic development, also known as animal embryogenesis, is the developmental stage of an animal embryo. Embryonic development starts with the fertilization of an egg cell (ovum) by a sperm, sperm cell (spermat ...
of certain tissues and organs, and for their maintenance, particularly
hematologic tissues, throughout life.
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s in ''PDGFRA'', are associated with an array of clinically significant
neoplasms
A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...
, notably ones of the
clonal hypereosinophilia
Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the cell growth, development and growth of a pre-malignant or malignant population of ...
class of malignancies, as well as
gastrointestinal stromal tumor
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior i ...
s (GISTs).
Overall structure
This gene encodes a typical
receptor tyrosine kinase
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinas ...
, which is a
transmembrane protein
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...
consisting of an extracellular ligand binding domain, a
transmembrane domain
A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...
and an intracellular tyrosine kinase domain. The
molecular mass
The molecular mass () is the mass of a given molecule, often expressed in units of daltons (Da). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The derived quan ...
of the mature, glycosylated PDGFRα protein is approximately 170 kDa. The protein is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family.
Modes of activation
Activation of PDGFRA requires de-repression of the receptor's kinase activity. The ligand for PDGFRα (PDGF) accomplishes this in the course of assembling a PDGFRα
dimer. Four of the five PDGF isoforms activate PDGFRα (
PDGF-A
Platelet-derived growth factor subunit A is a protein that in humans is encoded by the ''PDGFA'' gene.
The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factor ...
,
PDGF-B, PDGF-AB and
PDGF-C
Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein that in humans is encoded by the ''PDGFC'' gene. Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of ...
). The activated receptor
phosphorylates itself and other proteins, and thereby engages
intracellular signaling pathway
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term ...
s that trigger cellular responses such as migration and proliferation.
There are also PDGF-independent modes of de-repressing the PDGFRα's kinase activity and hence activating it. For instance, forcing PDGFRα into close proximity of each other by overexpression or with antibodies directed against the extracellular domain. Alternatively, mutations in the kinase domain that stabilize a kinase active conformation result in
constitutive activation
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recepto ...
. Finally, growth factors outside of the PDGF family (non-PDGFs) activate PDGFRα indirectly.
Non-PDGFs bind to their own receptors that trigger intracellular events that de-repress the kinase activity of PDGFRα monomers. The intracellular events by which non-PDGFs indirectly activate PDGFRα include elevation of
reactive oxygen species
In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...
that activate
Src family kinase
Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src (gene), Src, YES1, Yes, FYN, Fyn, and FGR (gene), Fgr, forming the SrcA subfamily, Lck, HCK, Hck, Tyrosine-protein kinase BLK, Blk, and Lyn (Src fam ...
s, which phosphorylate PDGFRα.
The mode of activation determines the duration that PDGFRα remains active. The PDGF-mediated mode, which dimerized PDGFRα, accelerates internalization and degradation of activated PDGFRα such that the half-life of PDGF-activated PDGFRα is approximately 5 min.
Enduring activation of PDGFRα (half-life greater than 120 min) occurs when PDGFRα monomers are activated.
Role in physiology/pathology
The importance of PDGFRA during development is apparent from the observation that the majority of mice lacking a functional ''Pdgfra'' gene develop a plethora of embryonic defects, some of which are lethal; the mutant mice exhibit defects in
kidney glomeruli
The glomerulus (: glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally suppor ...
because of a lack of
mesangial cell
Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately ...
s but also suffer an ill-defined blood defect characterized by
thrombocytopenic
In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coa ...
, a bleeding tendency, and severe anemia which could be due to blood loss. The mice die at or shortly before birth.
PDGF-A and PDGF-C seem to be the important activators of PDGFRα during development because mice lacking functional genes for both these PDGFRA activating ligands, i.e. ''Pdgfa''/''Pdgfc-'' double null mice show similar defects to ''Pdgra'' null mice.
Mice genetically engineered to express a constitutively (i.e. continuously) activated PDGFRα mutant receptor eventually develop fibrosis in the skin and multiple internal organs.
The studies suggest that PDGFRA plays fundamental roles in the development and function of
mesoderm
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...
al tissues, e.g., blood cells, connective tissue, and mesangial cells.
Clinical significance
PDGFRA mutations
Myeloid and lymphoid cells
Somatic mutations that cause the fusion of the ''PDGFRA'' gene with certain other genes occur in
hematopoietic stem cell
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...
s and cause a
hematological malignancy
Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all ...
in the
clonal hypereosinophilia
Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the cell growth, development and growth of a pre-malignant or malignant population of ...
class of malignancies. These mutations create
fused genes which encode
chimeric proteins that possess continuously active PDGFRA-derived
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
. They thereby continuously stimulate cell growth and proliferation and lead to the development of
leukemia
Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
s,
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
s, and
myelodysplastic syndromes
A myelodysplastic syndrome (MDS) is one of a group of cancers in which blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may includ ...
that are commonly associated with
hypereosinophilia and therefore regarded as a sub-type of clonal eosinophilia. In the most common of these mutations, the ''PDGFRA'' gene on human chromosome 4 at position q12 (notated as 4q12) fuses with the
FIP1L1
Factor interacting with PAPOLA and CPSF1 (i.e, FIP1L1; also termed Pre-mRNA 3'-end-processing factor FIP1) is a protein that in humans is encoded by the ''FIP1L1'' gene (also known as Rhe, FIP1, and hFip1). A medically important aspect of the ''F ...
gene also located at position 4q12. This interstitial (i.e. on the same chromosome) fusion creates a ''FIP1L1''-''PDGFRA'' fusion gene while usually losing intervening genetic material, typically including either the ''CHIC2'' or ''
LNX'' gene. The fused gene encodes a FIP1L1-PDGFRA protein that causes: a) chronic
eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 billion/ L (1,500/ μL). The hypereosinophilic syndrome ...
which progresses to
chronic eosinophilic leukemia
Chronic eosinophilic leukemia is a form of cancer in which too many eosinophils are found in the bone marrow, blood, and other tissues. Most cases are associated with fusion genes.
Signs and symptoms
Signs and symptoms may include weight loss, f ...
; b) a form of
myeloproliferative neoplasm
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. ''Myelo'' refers to the bone marrow, ''proliferative'' describes the rapid grow ...
/
myeloblastic leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include ...
associated with little or no eosinophilia; c)
T-lymphoblastic leukemia/lymphoma
T-lymphoblastic leukemia/lymphoma (WHO 2008), previously labeled precursor T-lymphoblastic leukemia/lymphoma (WHO 2001) is a form of lymphoid leukemia and lymphoma in which too many T-cell lymphoblasts (immature white blood cells) are found in the ...
associated with eosinophilia; d)
myeloid sarcoma with eosinophilia (see
''FIP1L1-PDGFRA'' fusion genes); or e) mixtures of these presentations. Variations in the type of malignancy formed likely reflects the specific type(s) of hematopoietic stem cells that bear the mutation.
The ''PDGFRA'' gene may also mutate through any one of several
chromosome translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...
s to create fusion genes which, like the ''Fip1l1-PDGFRA'' fusion gene, encode a fusion protein that possesses continuously active PDGFRA-related tyrosine kinase and causes myeloid and/or lymphoid malignancies. These mutations, including the ''Fip1l1-PDGFRA'' mutation, along with the chromosomal location of ''PDGFRAs partner and the notation used to identify the fused gene are given in the following table.
Patients afflicted with any one of these translocation mutations, similar to those afflicted with the interstitial ''PDGFRA-FIP1l1'' fusion gene: a) present with findings of chronic eosinophilia, hypereosinophilia, the hypereosinophilic syndrome, or chronic eosinophilic leukemia; myeloproliferative neoplasm/myeloblastic leukemia; a T-lymphoblastic leukemia/lymphoma; or myeloid sarcoma; b) are diagnosed cytogenetically, usually by analyses that detect breakpoints in the short arm of chromosome 4 using Fluorescence in situ hybridization
Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed by ...
; and c) where treated (many of the translocations are extremely rare and have not be fully tested for drug sensitivity), respond well or are anticipated to respond well to imatinib
Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...
therapy as described for the treatment of diseases caused by ''FIP1L1-PDGFRA'' fusion genes.[
]
Gastrointestinal tract
Activating mutations in PDGFRA are also involved in the development of 2–15% of gastrointestinal stromal tumors (GISTs), which is the most common mesenchymal neoplasm of the gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
. GIST tumors are sarcoma
A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues.
Sarcom ...
s derived from the GI tract's connective tissue whereas most GI tract tumors are adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
s derived from the tract's epithelium
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells. GIST tumors occur throughout the GI tract but most (66%) occur in the stomach and when developing there have a lower malignant potential than GIST tumors found elsewhere in the GI tract. The most common PDGFRA mutations found in GIST tumors occur in exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
18 and are thought to stabilize PDGFRA's tyrosine kinase in an activated conformation. A single mutation, D842V, in this exon accounts for >70% of GIST tumors. The next most common GIST tumor mutation occurs in exon 18, accounts for <1% of GISTs tumors, and is a deletion of codon
Genetic code is a set of rules used by living cells to translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished by the ribosome, which links prote ...
s 842 to 845. Exon 12 is the second most commonly mutated PDGFRA exon in GIST, being found in ~1% of GIST tumors. Mutations in PDGFRA's exon 14 are found in <1% of GIST tumors. While some ''PDGFRA'' mutation-induced GIST tumors are sensitive to the tyrosine kinase inhibitor, imatinib
Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...
, the most common mutation, D842V, as well as some very rare mutations are resistant to this drug: median overall survival is reported to be only 12.8 months in patients whose tumors bear the D842V mutation compared to 48–60 months in large series of imatinib-treated patients with other types of GIST mutations. Consequently, it is critical to define the exact nature of ''PDGFR''-induced mutant GIST tumors in order to select appropriate therapy particularly because a novel PDGFRA selective kinase inhibitor, crenolanib, is under investigation for treating D842V-induced and other imatinib-resistant GIST tumors. A randomized trial testing the efficacy of crenolanib in patients with GIST tumors bearing the D842V mutation is under recruitment.
Olaratumab (LY3012207) is a human IgG1 monoclonal antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodie ...
designed to bind to human PDGFRα with high affinity and block PDGF-AA, PDGF-BB, and PDGF-CC ligands from binding to the receptor. Numerous studies using it to treat soft tissue sarcomas including GIST are ongoing. Studies on GIST have focused on inoperable, metastatic, and/or recurrent disease and have tested olagatumab with Doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
versus doxorubicin along. The US FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
granted approval for the use of olaratumab-dcoxorbicin therapy of soft tissue sarcomas under its Accelerated Approval Program based on the results of the phase II trial, (NCT01185964). In addition, the European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
granted conditional approval for olaratumab in this indication in November 2016 following a review under the EMA's Accelerated Assessment Program.
Nervous system
Gain-of-function
Gain-of-function research (GoF research or GoFR) is medical research that genetically alters an organism in a way that may enhance the biological functions of gene products. This may include an altered pathogenesis, transmissibility, or host ran ...
H3K27M mutations in protein histone H3
Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal end, N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'b ...
lead to inactivation of polycomb repressive complex 2
PRC2 (polycomb repressive complex 2) is one of the two classes of polycomb-group proteins or (PcG). The other component of this group of proteins is PRC1 (Polycomb Repressive Complex 1).
This complex has histone methyltransferase activity and pr ...
(PRC2) methyltransferase
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ro ...
and result in global hypomethylation
Methylation, in the chemistry, chemical sciences, is the addition of a methyl group on a substrate (chemistry), substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replac ...
of H3K27me3
H3K27me3 is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein.
This tri-methylation is associated with the Downregulation and upregulation, down ...
and transcriptional derepression In genetics and cell biology, repression is a mechanism often used to decrease or inhibit the expression of a gene. Removal of repression is called derepression. This mechanism may occur at different stages in the expression of a gene, all resulting ...
of potential oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels. s. About 40% of these mutation are associated with gain of function or amplifications mutations in the ''PDGFRA'' gene in cases of pediatric diffuse Glioma
A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...
s of the pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other mammals, lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of ...
. It appears that the initial histone H3 mutations alone are insufficient but rather require cooperating secondary mutations such as ''PDGFRA''-activating mutations or ''PDGFRA'' amplifications to develop this type of brain tumor. In a small non-randomized trial study, imatinib therapy in patients with glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
selected on the basis of having imatinib-inhibitable tyrosine kinases in biopsy tissue caused marginal disease improvement compared to similar treatment of patients with unselected recurrent glioblastoma. This suggests that patient sub-populations with excessive PDGFRA-related or other tyrosine kinase-related over-activity might benefit from imatinib therapy. Several phase I and Phase II clinical glioma/glioblastoma studies have been conducted using imatinib but no decisive follow-up phase III studies have been reported.
Interactions
PDGFRA has been shown to interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with:
* CRK,
* Caveolin 1
Caveolin-1 is a protein that in humans is encoded by the ''CAV1'' gene.
Function
The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits ...
,
* Cbl gene
E3 ubiquitin-protein ligase CBL is an enzyme that is humans is encoded by the ''CBL'' (Casitas B-lineage Lymphoma) gene. ''CBL'' gene is the founding member the Cbl family. The protein CBL which is an Ubiquitin ligase, E3 ubiquitin-protein liga ...
,
* PDGFC
Platelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein that in humans is encoded by the ''PDGFC'' gene. Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of ...
,
* PDGFR-β,
* PLCG1, and
* Sodium-hydrogen antiporter 3 regulator 1
Sodium-hydrogen antiporter 3 regulator 1 (SLC9A3R1) is a human protein. It is a regulator of Sodium-hydrogen antiporter 3 and is encoded by the gene ''SLC9A3R1''. It is also known as ERM Binding Protein 50 (EBP50) or Na+/H+ Exchanger Regulatory ...
.
Notes
See also
* Platelet-derived growth factor receptor
Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellula ...
* Clonal eosinophilia
Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the development and growth of a pre-malignant or malignant population of eosinophil ...
References
Further reading
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Tyrosine kinase receptors