TET-2
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TET-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. An ex ...
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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: protein-coding genes and non-coding genes. During gene expression (the synthesis of Gene product, RNA or protein from a gene), DNA is first transcription (biology), copied into RNA. RNA can be non-coding RNA, directly functional or be the intermediate protein biosynthesis, template for the synthesis of a protein. The transmission of genes to an organism's offspring, is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype, that is specific to every given individual, within the gene pool of the population (biology), population of a given species. The genotype, along with environmental and developmental factors, ultimately determines the phenotype ...
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Thymine
Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. In RNA, thymine is replaced by the nucleobase uracil. Thymine was first isolated in 1893 by Albrecht Kossel and Albert Neumann from calf thymus glands, hence its name. Derivation As its alternate name (5-methyluracil) suggests, thymine may be derived by methylation of uracil at the 5th carbon. In RNA, thymine is replaced with uracil in most cases. In DNA, thymine (T) binds to adenine (A) via two hydrogen bonds, thereby stabilizing the nucleic acid structures. Thymine combined with deoxyribose creates the nucleoside deoxythymidine, which is synonymous with the term thymidine. Thymidine can be phosphorylated with up to three phosphoric acid groups, producing dTMP (deoxythymidine monophosphate), dTDP, or dTTP (for the ...
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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 locus (genetics), 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#Chromosomal determination, sex-determination system. If both alleles of a diploid organism are the same, the organism is #Homozygous, homozygous at that locus. If they are different, the organism is #Heterozygous, heterozygous at that locus. If one allele is missing, it is #Hemizygous, hemizygous, and, if both alleles are missing, it is #Nullizygous, nullizygous. The ...
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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 getting older, being male, 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 ...
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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 >1 billion/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be 10% and 1 billion/L is essent ...
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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, ...
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Myelodysplastic Syndrome
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 include fatigue, 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 (element), mercury or lead. Problems with blood cell formation result in some combination of low anemia, red blood cell, thrombocytopenia, platelet, and white blood cell counts. Some types of MDS cause an increase in the production of immature blood cells (called blast cell, blasts), in the bone marrow or peripheral blood, blood. The different types of MDS are identified based on the specific characteristics of the chang ...
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Somatic Evolution In Cancer
Somatic evolution is the accumulation of mutations and Epigenetic clock, 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 Cancer epigenetics, epimutations on the Fitness (biology), 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 Neoplasm#Malignant neoplasms, 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 Tumour heterogeneity, variation in the population. Neoplasms are mosaics of different mutant cells with both ...
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Chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA repair#DNA damage, DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin. The primary protein components of chromatin are histones. An octamer of two sets of four histone cores (Histone H2A, Histone H2B, Histone H3, and Histone H4) bind to DNA and function as "anchors" around which the strands are wound.Maeshima, K., Ide, S., & Babokhov, M. (2019). Dynamic chromatin organization without the 30 nm fiber. ''Current opinion in cell biolog ...
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Haematopoiesis
Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten billion () to a hundred billion () new blood cells are produced per day, 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 diff ...
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DNA Demethylation
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence (5mC will be diluted out). Methylated cytosine is frequently present in the linear DNA sequence where a cytosine is followed by a guanine in a Directionality (molecular biology), 5' → 3' direction (a CpG site). In mammals, DNA methyltransferases (which add methyl groups to DNA bases) exhibit a strong sequence preference for cytosines at CpG sites. There appear to be more than 20 million CpG dinucleotides in the human genome (see CpG site#Genomic distribution, genomic distribution). In mammals, on average, 70% to 80% of CpG cytosines are methylated, though the level of methylation varies with ...
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Neoplasm
A neoplasm () is a type of abnormal and excessive growth of 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 tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.'' ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, such as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word neoplasm is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm ...
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