Leukemia-Lymphoma, Adult T-Cell: Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.Precursor Cell Lymphoblastic Leukemia-Lymphoma: A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.Dihydrouracil Dehydrogenase (NAD+)Precursor B-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.Deltaretrovirus: A genus in the family RETROVIRIDAE consisting of exogenous horizontally-transmitted viruses found in a few groups of mammals. Infections caused by these viruses include human B- or adult T-cell leukemia/lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), and bovine leukemia (ENZOOTIC BOVINE LEUKOSIS). The type species is LEUKEMIA VIRUS, BOVINE.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Leukemia, B-Cell: A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.Leukemia: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)Human T-lymphotropic virus 1: A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).Protein PrecursorsT-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Oligodendroglia: A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.Vulva: The external genitalia of the female. It includes the CLITORIS, the labia, the vestibule, and its glands.Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Neural Stem Cells: Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.RNA Precursors: RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.Erythroid Precursor Cells: The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.Nestin: A type VI intermediate filament protein expressed mostly in nerve cells where it is associated with the survival, renewal and mitogen-stimulated proliferation of neural progenitor cells.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Mice, Inbred C57BLBase Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Neurogenesis: Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Nerve Tissue ProteinsImmunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Basic Helix-Loop-Helix Transcription Factors: A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neuroglia: The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Precursor Cells, T-Lymphoid: Lymphocyte progenitor cells that are restricted in their differentiation potential to the T lymphocyte lineage.Nucleic Acid Precursors: Use for nucleic acid precursors in general or for which there is no specific heading.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Monocyte-Macrophage Precursor Cells: Parent cells in the lineage that gives rise to MONOCYTES and MACROPHAGES.Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Astrocytes: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Intermediate Filament Proteins: Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin, decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein.Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.Embryo, Nonmammalian: The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.Embryo, Mammalian: The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Embryonic Induction: The complex processes of initiating CELL DIFFERENTIATION in the embryo. The precise regulation by cell interactions leads to diversity of cell types and specific pattern of organization (EMBRYOGENESIS).Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Myoblasts: Embryonic (precursor) cells of the myogenic lineage that develop from the MESODERM. They undergo proliferation, migrate to their various sites, and then differentiate into the appropriate form of myocytes (MYOCYTES, SKELETAL; MYOCYTES, CARDIAC; MYOCYTES, SMOOTH MUSCLE).Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Morphogenesis: The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Stem Cell Transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Body Patterning: The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.Myelin Sheath: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell SeparationMesoderm: The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Hematopoiesis: The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Animals, Newborn: Refers to animals in the period of time just after birth.Nervous System: The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)Caenorhabditis elegans Proteins: Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS.Sense Organs: Specialized organs adapted for the reception of stimuli by the NERVOUS SYSTEM.Cerebral Ventricles: Four CSF-filled (see CEREBROSPINAL FLUID) cavities within the cerebral hemispheres (LATERAL VENTRICLES), in the midline (THIRD VENTRICLE) and within the PONS and MEDULLA OBLONGATA (FOURTH VENTRICLE).Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Embryonic Stem Cells: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Brain Tissue Transplantation: Transference of brain tissue, either from a fetus or from a born individual, between individuals of the same species or between individuals of different species.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Hedgehog Proteins: A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Animals, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.Telencephalon: The anterior subdivision of the embryonic PROSENCEPHALON or the corresponding part of the adult prosencephalon that includes the cerebrum and associated structures.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Colony-Forming Units Assay: A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.Muscle Development: Developmental events leading to the formation of adult muscular system, which includes differentiation of the various types of muscle cell precursors, migration of myoblasts, activation of myogenesis and development of muscle anchorage.Spleen: An encapsulated lymphatic organ through which venous blood filters.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Paired Box Transcription Factors: A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Coturnix: A genus of BIRDS in the family Phasianidae, order GALLIFORMES, containing the common European and other Old World QUAIL.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.MyoD Protein: A myogenic regulatory factor that controls myogenesis. Though it is not clear how its function differs from the other myogenic regulatory factors, MyoD appears to be related to fusion and terminal differentiation of the muscle cell.Kinetics: The rate dynamics in chemical or physical systems.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.Granulocyte Precursor Cells: The cells in the granulocytic series that give rise to mature granulocytes (NEUTROPHILS; EOSINOPHILS; and BASOPHILS). These precursor cells include myeloblasts, promyelocytes, myelocytes and metamyelocytes.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Erythropoiesis: The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.Neural Crest: The two longitudinal ridges along the PRIMITIVE STREAK appearing near the end of GASTRULATION during development of nervous system (NEURULATION). The ridges are formed by folding of NEURAL PLATE. Between the ridges is a neural groove which deepens as the fold become elevated. When the folds meet at midline, the groove becomes a closed tube, the NEURAL TUBE.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Optic Nerve: The 2nd cranial nerve which conveys visual information from the RETINA to the brain. The nerve carries the axons of the RETINAL GANGLION CELLS which sort at the OPTIC CHIASM and continue via the OPTIC TRACTS to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the SUPERIOR COLLICULI and the SUPRACHIASMATIC NUCLEI. Though known as the second cranial nerve, it is considered part of the CENTRAL NERVOUS SYSTEM.Regeneration: The physiological renewal, repair, or replacement of tissue.
Adult T-cell leukemia/lymphomaThe Simon Flavell Leukaemia Research Laboratory: The Simon Flavell Leukaemia Research Laboratory is based at Southampton General Hospital and named after ten-year-old Simon Flavell who died in 1990 from an aggressive form of T-cell acute lymphoblastic leukaemia (ALL). The laboratory specialises in researching and developing antibody type treatments for adults and children with currently incurable types of leukaemia.DihydrouracilWorld Lymphoma Awareness Day: World Lymphoma Awareness Day (WLAD) is held on September 15 every year and is a day dedicated to raising awareness of lymphoma, an increasingly common form of cancer. It is a global initiative hosted by the Lymphoma Coalition (LC), a non-profit network organisation of 63 lymphoma patient groups from 44 countries around the world.Pre-B-cell leukemia homeobox: Pre-B-cell leukemia homeobox (PBX) refers to a family of transcription factors.Childhood leukemia: Childhood leukemia is a type of leukemia, usually acute lymphocytic leukemia (ALL), and a type of childhood cancer. The cure rate of childhood leukemia is generally higher than adult leukemia, approaching 90%, although some side effects of treatment last into adulthood.Human T-lymphotropic virus: The human T-lymphotropic virus or human T-cell lymphotropic virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult T-cell leukemia/lymphoma and a demyelinating disease called HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLVs belong to a larger group of primate T-lymphotropic viruses (PTLVs).PMHC cellular microarray: PMHC cellular microarrays are a type of cellular microarray that has been spotted with pMHC complexes peptide-MHC class I or peptide-MHC class II.Renal stem cell: Renal stem cells are self-renewing, multipotent stem cells which are able to give rise to all the cell types of the kidney. It is involved in the homeostasis and repair of the kidney, and holds therapeutic potential for treatment of kidney failure.Amyloid precursor proteinGliogenesis: Gliogenesis is the generation of non-neuronal glia populations derived from multipotent neural stem cells.Lineage markers: The lineage markers are characteristic molecules for cell lineages, e.g.HSD2 neurons: HSD2 neurons are a small group of neurons in the brainstem which are uniquely sensitive to the mineralocorticosteroid hormone aldosterone, through expression of HSD11B2. They are located within the caudal medulla oblongata, in the nucleus of the solitary tract (NTS).Myeloid: The term myeloid (myelogenous) is an adjective that can refer to a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets. Myeloid can be distinguished from the lymphoid progenitor cells that give rise to B cells and T cells.Zymogen: A zymogen (or proenzyme) is an inactive enzyme precursor. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the active site) for it to become an active enzyme.Coles PhillipsSymmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.P7C3MinC: The MinC protein is one of three proteins encoded by the minB operon and which is required to generate pole to pole oscillations prior to bacterial cell division as a means of specifying the midzone of the cell. This function is achieved by preventing the formation of the divisome Z-ring around the poles.Pituitary-specific positive transcription factor 1: POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone.Iroquois homeobox factor: Iroquois homeobox factors are a family of homeodomain transcription factors that play a role in many developmental processes.Brain healing: Brain healing is the process that occurs after the brain has been damaged. If an individual survives brain damage, the brain has a remarkable ability to adapt.Mature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.Haptotaxis: Haptotaxis (from Greek ἅπτω (hapto, "touch, fasten") and τάξις (taxis, "arrangement, order")) is the directional motility or outgrowth of cells, e.g.Notch signaling pathway: The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms.Neuromorphology: Neuromorphology (from Greek νεῦρον, neuron, "nerve"; μορφή, morphé, “form”; -λογία, -logia, “study of”[is the study of nervous system] form, shape, and structure. The study involves looking at a particular part of the nervous system from a [[Molecular biology|molecular and cellular level and connecting it to a physiological and anatomical point of view.Amyloid precursor protein secretase: Secretases are enzymes that "snip" pieces off a longer protein that is embedded in the cell membrane.[of the amyloid precursor protein] Among other roles in the cell, secretases act on the amyloid precursor protein (APP) to cleave the protein into three fragments.Astrocyte: Astrocytes (Astro from Greek astron = star and cyte from Greek "kyttaron" = cell), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. The proportion of astrocytes in the brain is not well defined.Bone marrow suppression: Bone marrow suppression or myelotoxicity (adjective myelotoxic) or myelosuppression is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine.Phenotype microarray: The phenotype microarray approach is a technology for high-throughput phenotyping of cells.KIAA0895L: Uncharacterized protein KIAA0895-like also known as LOC653319, is a protein that in humans is encoded by the KIAA0895L gene.Membrane protein: Membrane proteins are proteins that interact with biological membranes. They are one of the common types of protein along with soluble globular proteins, fibrous proteins, and disordered proteins.BESS domain: In molecular biology, the BESS domain is a protein domain which has been named after the three proteins that originally defined the domain: BEAF (Boundary element associated factor 32), Suvar(3)7 and Stonewall ). The BESS domain is 40 amino acid residues long and is predicted to be composed of three alpha helices, as such it might be related to the myb/SANT HTH domain.OsteoclastSynapto-pHluorin: Synapto-pHluorin is a genetically encoded optical indicator of vesicle release and recycling. It is used in neuroscience to study transmitter release.DNA-binding proteinFlow cytometry: In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.Glial fibrillary acidic protein: Glial fibrillary acidic protein (GFAP) is a protein that is encoded by the GFAP gene in humans.Multiple patterning: Multiple patterning (or multi-patterning) is a class of technologies for manufacturing integrated circuits (ICs), developed for photolithography to enhance the feature density. The simplest case of multiple patterning is double patterning, where a conventional lithography process is enhanced to produce double the expected number of features.Remyelination: Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the CNS. This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS.Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingMesenchyme: Mesenchyme is a type of tissue characterized by loosely associated cells that lack polarity and are surrounded by a large extracellular matrix. Mesenchymal cells are able to develop into the tissues of the lymphatic and circulatory systems, as well as connective tissues throughout the body, such as bone and cartilage.Hassall's corpuscles: Hassall's corpuscles (or thymic corpuscles (bodies)) are structures found in the medulla of the human thymus, formed from eosinophilic type VI epithelial reticular cells arranged concentrically. These concentric corpuscles are composed of a central mass, consisting of one or more granular cells, and of a capsule formed of epithelioid cells.Drosophila embryogenesis: Drosophila embryogenesis, the process by which Drosophila (fruit fly) embryos form, is a favorite model system for geneticists and developmental biologists studying embryogenesis. The small size, short generation time, and large brood size make it ideal for genetic studies.History of research on Caenorhabditis elegans: The nematode worm Caenorhabditis elegans was first studied in the laboratory by Victor Nigon and Ellsworth Dougherty in the 1940s, but came to prominence after being adopted by Sydney Brenner in 1963 as a model organism for the study of developmental biology using genetics. In 1974, Brenner published the results of his first genetic screen, which isolated hundreds of mutants with morphological phenotypes.Human embryonic stem cells clinical trials: ==Human Embryonic Stem Cell Clinical Trials==Hes3 signaling axis: The STAT3-Ser/Hes3 signaling axis is a specific type of intracellular signaling pathway that regulates several fundamental properties of cells.
(1/3678) Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter.
A cytogenetically cryptic (12;21) translocation is the most common molecular abnormality identified in childhood acute lymphoblastic leukemia (ALL), and it generates a chimeric TEL-AML1 protein. Fusion of the Helix-Loop-Helix (HLH) (also called the pointed) domain of TEL to AML1 has been suggested to convert AML1 from a transcriptional activator to a repressor. To define the structural features of this chimeric protein required for repression, we analysed the transcriptional activity of a series of TEL-AML1 mutants on the AML1-responsive interleukin-3 (IL-3) promoter, a potentially relevant gene target. Our results demonstrate that TEL-AML1 represses basal IL-3 promoter activity in lymphoid cells, and deletion mutant analysis identified three distinct domains of TEL-AML1 that are required for repression; the HLH (pointed) motif contained in the TEL portion of TEL-AML1, and both the runt homology domain (Rhd) and the 74 amino acids downstream of the Rhd that are present in the AML1 portion of the fusion protein. Although AML1B (and a shorter AML1 isoform, AML1A) have transcriptional activating activity on the IL-3 promoter, fusion of the AML1 gene to the TEL gene generates a repressor of IL-3 expression. Consistent with this activity, freshly isolated human ALL cells that contain TEL-AML1 do not express IL-3. (+info)
(2/3678) Evidence of space-time clustering of childhood acute lymphoblastic leukaemia in Sweden.
We have examined 645 recorded cases of childhood acute lymphatic leukaemia (ALL) in Sweden during 1973-89 to identify space-time clustering by using the close-pair method of Knox. The records included date of birth and of diagnosis as well as addresses at birth and at diagnosis. There was a significant excess of case pairs close in date of birth and place of birth in the 5- to 15-year age group. (+info)
(3/3678) Patterns of care and survival for adolescents and young adults with acute leukaemia--a population-based study.
We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group. (+info)
(4/3678) Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms.
Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, factors governing susceptibility to this disease have not yet been identified. As such, ALL offers a useful opportunity to examine the glutathione S-transferase and cytochrome P450 genes in determining susceptibility to pediatric cancers. Both enzymes are involved in carcinogen metabolism and have been shown to influence the risk a variety of solid tumors in adults. To determine whether these genes played a similar role in childhood leukemogenesis, we compared the allele frequencies of 177 childhood ALL patients and 304 controls for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French population of Quebec as our study population because of its relative genetic homogeneity. The GSTM1 null and CYP1A1*2A genotypes were both found to be significant predictors of ALL risk (odds ratio [OR] = 1.8). Those possessing both genotypes were at an even greater risk of developing the disease (OR = 3.3). None of the other alleles tested for proved to be significant indicators of ALL risk. Unexpectedly, girls carrying the CYP1A1*4 were significantly underrepresented in the ALL group (OR = 0.2), suggesting that a gender-specific protective role exists for this allele. These results suggest that the risk of ALL may indeed be associated with xenobiotics-metabolism, and thus with environmental exposures. Our findings may also explain, in part, why ALL is more prevalent among males than females. (+info)
(5/3678) Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors.
The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%. The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events. Three hundred and one consecutive leukemic children were enrolled in this study. Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor: 20 children showed the TT677 MTHFR genotype; 5 showed the heterozygous prothrombin G20210A variant; 11 were carriers of the factor V G1691A mutation (heterozygous, n = 10; homozygous, n = 1); 4 showed familial protein C, 4 protein S, and 2 antithrombin type I deficiency; 9 patients were suffering from familially increased lipoprotein (a) [Lp(a)] concentrations (>30 mg/dL). In addition, combined prothrombotic defects were found in a further 10 patients: the FV mutation was combined with the prothrombin G20210A variant (n = 1), increased Lp(a) (n = 3), protein C deficiency (n = 1), and homozygosity for the C677T MTHFR gene mutation (n = 1). Lp(a) was combined with protein C deficiency (n = 2) and the MTHFR TT 677 genotype (n = 2). Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis. In 32 (11%) of these 289 patients venous thromboembolism occurred. The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system (P <.0001). In addition, a clear-cut positive correlation (P <.0001) was found between thrombosis and the use of central lines. However, because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals, the interaction between prothrombotic risk factors, ALL treatment, and further environmental factors is likely to cause thrombotic manifestations. (+info)
(6/3678) Reduced folate carrier expression in acute lymphoblastic leukemia: a mechanism for ploidy but not lineage differences in methotrexate accumulation.
Methotrexate (MTX) is one of the most active and widely used agents for the treatment of acute lymphoblastic leukemia (ALL). To elucidate the mechanism for higher accumulation of MTX polyglutamates (MTX-PG) in hyperdiploid ALL and lower accumulation in T-lineage ALL, expression of the reduced folate carrier (RFC) was assessed by reverse transcription-polymerase chain reaction in ALL blasts isolated from newly diagnosed patients. RFC expression exhibited a 60-fold range among 29 children, with significantly higher expression in hyperdiploid B-lineage ALL (median, 11.3) compared with nonhyperdiploid ALL (median, 2.1; P <.0006), but no significant difference between nonhyperdiploid B-lineage and T-lineage ALL. Furthermore, mRNA levels of RFC (mapped by FISH to chromosome 21) were significantly related to chromosome 21 copy number (P =.0013), with the highest expression in hyperdiploid ALL blasts with 4 copies of chromosome 21. To assess the functional significance of gene copy number, MTX-PG accumulation was compared in ALL blasts isolated from 121 patients treated with either low-dose MTX (LDMTX; n = 60) or high-dose MTX (HDMTX; n = 61). After LDMTX, MTX-PG accumulation was highest in hyperdiploid B-lineage ALL with 4 copies of chromosome 21 (P =.011), but MTX-PG accumulation was not significantly related to chromosome 21 copy number after HDMTX (P =.24). These data show higher RFC expression as a mechanism for greater MTX accumulation in hyperdiploid B-lineage ALL and indicate that lineage differences in MTX-PG accumulation are not due to lower RFC expression in T-lineage ALL. (+info)
(7/3678) Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia.
Inefficient polyglutamylation is a mechanism of resistance to methotrexate (MTX) in childhood T-lineage acute lymphoblastic leukemia (T-ALL) and in acute myeloid leukemia (AML) in comparison with childhood c/preB-ALL. We analyzed the profile of MTX polyglutamylation in childhood c/preB-ALL, T-ALL, and AML (n = 45, 15, and 14, respectively), the activity of the MTX-polyglutamate synthesizing enzyme folylpolyglutamate synthetase (FPGS) (n = 39, 11, and 19, respectively) and of the MTX-polyglutamate breakdown enzyme folylpolyglutamate hydrolase (FPGH) (n = 98, 25, and 34, respectively). MTX-Glu4-6 accumulation after 24 hours exposure to 1 micromol/L [3H]-MTX in vitro was lower in T-ALL (threefold) and AML (fourfold) compared with c/preB-ALL (P =.001). The FPGS activity was twofold lower in T-ALL and AML than in c/preB-ALL samples (P <. 01). FPGH activity was not different between c/preB-ALL and T-ALL, but threefold higher in AML (P <.001). FPGS, FPGH, and the ratio FPGS/FPGH were correlated with MTX-Glu4-6 accumulation (r =.49, r = -.34 and r =.61, respectively). Multivariate analysis showed that FPGS, but not FPGH, was an independent contributor for MTX-Glu1-6 accumulation, but not for MTX-Glu4-6 accumulation. In conclusion, low FPGS activity is associated with low accumulation of MTX-Glu4-6 in T-ALL and AML. For the group of AML as compared with the group of ALL, a high FPGH activity can play an additional role. (+info)
(8/3678) A requirement for protein kinase C inhibition for calcium-triggered apoptosis in acute lymphoblastic leukemia cells.
We have evaluated the cytotoxicities of the combinations of calcium mobilizers and PKC inhibitors against human acute lymphoblastic leukemia (ALL) cells. Here we report that calcium mobilizers alone or PKC inhibitors alone do not induce apoptosis in human ALL cells. However, the combinations of calcium mobilizers with potent inhibitors of PKC cause significant apoptosis in ALL cells. Our results provide experimental evidence that PKC blocks Ca2+-triggered apoptosis in human ALL cells. Thus, PKC inhibitors can be used to enhance the antileukemic activity of chemical or biological agents that trigger an apoptotic calcium signal in ALL cells. The exquisite sensitivity of ALL cells to calcium-dependent apoptosis in the presence of PKC inhibitors could provide the basis for new treatment programs against ALL. (+info)