Ten-Eleven Translocation 2
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Ten-Eleven Translocation 2
Tet methylcytosine dioxygenase 2 (''TET2'') is a human gene. It resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Function ''TET2'' encodes a protein that catalyzes the conversion of the modified DNA base methylcytosine to 5-hydroxymethylcytosine. The first mechanistic reports showed tissue-specific accumulation of 5-hydroxymethylcytosine ( 5hmC) and the conversion of 5mC to 5hmC by TET1 in humans in 2009. In these two papers, Kriaucionis and Heintz provided evidence that a high abundance of 5hmC can be found in specific tissues and Tahiliani et al. demonstrated the TET1-dependent conversion of 5mC to 5hmC. A role for TET1 in cancer was reported in 2003 showing that it acted as a complex with MLL (myeloid/lymphoid or mixed-lineage leukaemia 1) (KMT2A), a positive global regulator of gene transcription that is named after its role cancer regulation. ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and 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: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Substrate (chemistry)
In chemistry, the term substrate is highly context-dependent. Broadly speaking, it can refer either to a chemical species being observed in a chemical reaction, or to a surface on which other chemical reactions or microscopy are performed. In the former sense, a reagent is added to the ''substrate'' to generate a product through a chemical reaction. The term is used in a similar sense in synthetic and organic chemistry, where the substrate is the chemical of interest that is being modified. In biochemistry, an enzyme substrate is the material upon which an enzyme acts. When referring to Le Chatelier's principle, the substrate is the reagent whose concentration is changed. ;Spontaneous reaction : :*Where S is substrate and P is product. ;Catalysed reaction : :*Where S is substrate, P is product and C is catalyst. In the latter sense, it may refer to a surface on which other chemical reactions are performed or play a supporting role in a variety of spectroscopic and microsco ...
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Lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night. Many subtypes of lymphomas are known. The two main categories of lymphomas are the non-Hodgkin lymphoma (NHL) (90% of cases) and Hodgkin lymphoma (HL) (10%). The World Health Organization (WHO) includes two other categories as types of lymphoma – multiple myeloma and immunoproliferative diseases. Lymphomas and leukemias are a part of the broader group of tumors of the hematopoietic and lymphoid tissues. Risk factors for Hodgkin lymphoma include infection with Epstein–Barr virus and a history of the disease in the family. Risk factors for common ...
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Immunodeficiency
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID. In clinical settings, immunosuppression by some drugs, such as steroids, can either be an adverse effect or the intended purpose of the treatment. Examples of such use is in organ transplant surgery as an anti- rejection measure and in patients with an overactive immune system, as in autoimmune diseases. Some people are born with intrinsic defects in their immune system, or primary immunodeficiency. A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised individual may particular ...
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Germline Mutation
A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and ova). Mutations in these cells are the only mutations that can be passed on to offspring, when either a mutated sperm or oocyte come together to form a zygote. After this fertilization event occurs, germ cells divide rapidly to produce all of the cells in the body, causing this mutation to be present in every somatic and germline cell in the offspring; this is also known as a constitutional mutation. Germline mutation is distinct from somatic mutation. Germline mutations can be caused by a variety of endogenous (internal) and exogenous (external) factors, and can occur throughout zygote development. A mutation that arises only in germ cells can result in offspring with a genetic condition that is not present in either parent; this is because the mutation is not present in the rest of the parents' body, only the germline. When mutagenesis oc ...
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Zygosity
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same loci on each of their two sets of homologous chromosomes except that the sequences at these loci may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a chromosomal sex-determination system. If both alleles of a diploid organism are the same, the organism is homozygous at that locus. If they are different, the organism is heterozygous at that locus. If one allele is missing, it is hemizygous, and, if both alleles are missing, it is nullizygous. The DNA sequence of a gene often varies from one individual to another. These gene variants are called alleles. While some gen ...
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Acute Myeloid Leukaemia
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 feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and outcomes may vary. The first-li ...
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Chronic Myelomonocytic Leukaemia
Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell. CMML shows characteristics of a myelodysplastic syndrome (MDS); a disorder that produces abnormal looking blood cells, and a myeloproliferative neoplasm (MPN); a disorder characterised by the overproduction of blood cells. For this reason, CMML was reclassified as a MDS/MPN overlap disorder in 2002. For a diagnosis of CMML, the World Health Organization (WHO) states that the blood monocyte count must be >1x109/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be 10% and 1x109/L is essential for a ...
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Myeloproliferative Neoplasms
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 growth of blood cells and ''neoplasm'' describes that growth as abnormal and uncontrolled. The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers. In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia. Classification MPNs are classified as blood cancers by most institutions and organizations. In MPNs, the neoplasm (abnormal growth) starts out as benign and can later become malignant. As of 2016, the World Health Organization lists the following subcategories of MPNs: * Chronic myeloid leukemia (CML) * Chronic neutrophilic leukemia (CNL) * Polycythemia vera (PV) * Primary myelofibrosis (PMF) ** PMF, Prefib ...
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Myelodysplastic Syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature 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 include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia. Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cell, platelet, and white blood cell counts. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. The types of MDS are based on specific changes in the blood cells and bone marrow. Treatments may include supportive care, drug therapy, and hematopoietic stem cell transplantati ...
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Somatic Evolution In Cancer
Somatic evolution is the accumulation of mutations and epimutations in somatic cells (the cells of a body, as opposed to germ plasm and stem cells) during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer. Natural selection in cancer Cells in pre-malignant and malignant neoplasms (tumors) evolve by natural selection. This accounts for how cancer develops from normal tissue and why it has been difficult to cure. There are three necessary and sufficient conditions for natural selection, all of which are met in a neoplasm: # There must be variation in the population. Neoplasms are mosaics of different mutant cells with both genetic and epigenetic changes that distinguish them from normal cells. # The variable traits must be h ...
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Haematopoiesis
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately – new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.Semester 4 medical lectures at Uppsala University 2008 by Leif Jansson Process Haematopoietic stem cells (HSCs) Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues. HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted. This phenomenon is called asymmetric division. The other daughters of HSCs ( myeloid and lymphoid progenitor cells) can follow any of the other ...
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