CD135
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CD135
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the ''FLT3'' gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L). It is expressed on the surface of many hematopoietic progenitor cells. Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells. The FLT3 gene is one of the most frequently mutated genes in acute myeloid leukemia (AML). High levels of wild-type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations. These high levels may be associated with worse prognosis. Structure FLT3 is composed of five extracellular immunoglobulin-like domains, an extracellular domain, a transmembrane domain, a juxtamembrane domain and a tyrosine-kinase ...
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FLT3
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the ''FLT3'' gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L). It is expressed on the surface of many hematopoietic progenitor cells. Signalling of FLT3 is important for the normal development of haematopoietic stem cells and progenitor cells. The FLT3 gene is one of the most frequently mutated genes in acute myeloid leukemia (AML). High levels of wild-type FLT3 have been reported for blast cells of some AML patients without FLT3 mutations. These high levels may be associated with worse prognosis. Structure FLT3 is composed of five extracellular immunoglobulin-like domains, an extracellular domain, a transmembrane domain, a juxtamembrane domain and a tyrosine-kinase ...
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Cluster Of Differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371 (). Nomenclature The CD nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), which was held in Paris in 1982. This system was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the ...
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Midostaurin
Midostaurin, sold under the brand name Rydapt & Tauritmo both by Novartis, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium ''Streptomyces staurosporeus''. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. AML and MDS Midostaurin was found to be active against oncogenic CD135 (FMS-like tyrosine kinase 3 receptor, FLT3), in preclinical studies. Clinical trials have primarily focused on relapsed/refractory AML and MDS and have included single agent and combination agent studies. After successful Phase II clinical trials, midostaurin was found to prolong survival of FLT3-mutated AML patients when combined with conventional induction and consolidation therapies in a randomized Phase III clinical trial. On April 28, 2017, ...
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Quizartinib
Quizartinib (AC220) is a small molecule receptor tyrosine kinase inhibitor, originally from Ambit Biosciences and later acquired by Daiichi Sankyo, that is currently under development for the treatment of acute myeloid leukaemia. Quizartinib is sold under the brand name Vanflyta in Japan. Its molecular target is FLT3, also known as CD135 which is a proto-oncogene. Flt3 mutations are among the most common mutations in acute myeloid leukaemia due to internal tandem duplication of Flt3. The presence of this mutation is a marker of adverse outcome. __TOC__ Mechanism Specifically, quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/ FMS), stem cell factor receptor (SCFR/ KIT), and platelet derived growth factor receptors (PDGFR Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth facto ...
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FMS-like Tyrosine Kinase 3 Ligand
Fms-related tyrosine kinase 3 ligand (FLT3LG) is a protein which in humans is encoded by the ''FLT3LG'' gene. Flt3 ligand (FL) is a hematopoietic four helical bundle cytokine. It is structurally homologous to stem cell factor (SCF) and colony stimulating factor 1 ( CSF-1). In synergy with other growth factors, Flt3 ligand stimulates the proliferation and differentiation of various blood cell progenitors. For example, it is a major growth factor stimulating the growth of dendritic cells. FLT3L functions as a cytokine and growth factor that increases the number of immune cells (lymphocytes (B cells and T cells)) by activating the hematopoietic progenitors. It acts by binding to and activating FLT3 (CD135) which is found on what (in mice) are called multipotent progenitor (MPP) and common lymphoid progenitor (CLP) cells. It also induces the mobilization of the hematopoietic progenitors and stem cells in vivo which may help the system to kill cancer cells. FLT3L is crucial for stea ...
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Immunoglobulin Domain
The immunoglobulin domain, also known as the immunoglobulin fold, is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino acids. The backbone switches repeatedly between the two β-sheets. Typically, the pattern is (N-terminal β-hairpin in sheet 1)-(β-hairpin in sheet 2)-(β-strand in sheet 1)-(C-terminal β-hairpin in sheet 2). The cross-overs between sheets form an "X", so that the N- and C-terminal hairpins are facing each other. Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin, and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein–protein and protein–ligand interactions. Examples Human genes encoding proteins containing the immunoglobulin domain include: * A1BG * ACAM * ADAMTSL1 * ADAMTSL3 * AGER * A ...
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Flt3L
Fms-related tyrosine kinase 3 ligand (FLT3LG) is a protein which in humans is encoded by the ''FLT3LG'' gene. Flt3 ligand (FL) is a haematopoiesis, hematopoietic four helical bundle cytokine. It is structurally homologous to stem cell factor (SCF) and colony stimulating factor 1 (Macrophage colony-stimulating factor, CSF-1). In synergy with other growth factors, Flt3 ligand stimulates the proliferation and differentiation of various blood cell progenitor cell, progenitors. For example, it is a major growth factor stimulating the growth of dendritic cells. FLT3L functions as a cytokine and growth factor that increases the number of immune cells (lymphocytes (B cells and T cells)) by activating the hematopoietic progenitors. It acts by binding to and activating FLT3 (CD135) which is found on what (in mice) are called multipotent progenitor (MPP) and common lymphoid progenitor (CLP) cells. It also induces the mobilization of the hematopoietic progenitors and stem cells in vivo which ...
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Leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ''leukemia cells''. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy. The exact cause of leukemia is unknown. A combination of genetic factors and environmental (non-inherited) factors are believed to play a role. Risk factors include smoking, ionizing radiation, petrochemicals (such as benzene), prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. There are four main types of leukemia— acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloi ...
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Common Lymphoid Progenitor
Lymphopoiesis (lĭm'fō-poi-ē'sĭs) (or lymphocytopoiesis) is the generation of lymphocytes, which are one of the five types of white blood cells (WBCs). It is more formally known as lymphoid hematopoiesis. Disruption in lymphopoiesis can lead to a number of lymphoproliferative disorders, such as the lymphomas and lymphoid leukemias. Terminology Lymphocytes are considered to be of the lymphoid lineage as opposed to other lineages of blood cells such as the myeloid lineage and the erythroid lineage. Nomenclature, the system of naming things properly, is not trivial in this case because although lymphocytes are found in the bloodstream and originate in the bone marrow, they principally belong to the separate lymphatic system which interacts with the blood circulation. Lymphopoiesis is now usually used interchangeably with the term "lymphocytopoiesis" - the making of lymphocytes - but other sources may distinguish between the two, stating that "lymphopoiesis" additionally refe ...
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Proto-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.Kimball's Biology Pages.
"Oncogenes" Free full text
Most normal cells will undergo a programmed form of rapid cell death ( apoptosis) when critical functions are altered and malfunctioning. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead. Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they will predispose the cell to cancer; thus, th ...
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Mutations
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, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication (translesion synthesis). Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutation is the ultimate source o ...
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Gilteritinib
Gilteritinib, sold under the brand name Xospata, is an anti-cancer drug. It acts as an inhibitor of FLT3, hence it is a tyrosine kinase inhibitor. It was developed by Astellas Pharma. In April 2018, Astellas filed a new drug application with the Food and Drug Administration for gilteritinib for the treatment of adult patients with FLT3 mutation–positive relapsed or refractory acute myeloid leukemia (AML). In November 2018, the FDA approved gilteritinib for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. Gilteritinib was granted orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ... status by the U.S. FDA, the European Commission (EC) and the Japan Ministry of Health, L ...
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