Notch signaling pathwayThe Notch signaling pathway is a highly conserved cell signaling system present in most animals. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein. It is a hetero-oligomer composed of a large extracellular portion, which associates in a calcium-dependent, non-covalent interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small intracellular region.
Chronic lymphocytic leukemiaChronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years. Risk factors include having a family history of the disease, with 10% of those who develop CLL having a family history of the disease.
Cell signalingIn biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes. Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas).
LeukemiaLeukemia (also spelled leukaemia and pronounced luːˈkiːmiːə ) 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.
Hematopoietic stem cellHematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.
Regulation of gene expressionRegulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein.
Lymphoid leukemiaLymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cell. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma). Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.
B-cell lymphomaThe B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured.
Bone marrowBone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.
Large granular lymphocytic leukemiaLarge granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood. It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells). In a study based in the US, the average age of diagnosis was 66.
T-cell prolymphocytic leukemiaT-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include T-cell chronic lymphocytic leukemia, "knobby" type of T-cell leukemia, and T-prolymphocytic leukemia/T-cell lymphocytic leukemia.
Gene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA.
Haematopoietic systemThe haematopoietic system is the system in the body involved in the creation of the cells of blood. Hematopoietic stem cell 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.
Epithelial–mesenchymal transitionThe epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.
Knockout mouseA knockout mouse, or knock-out mouse, is a genetically modified mouse (Mus musculus) in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.
Juxtacrine signallingIn biology, juxtacrine signalling (or contact-dependent signalling) is a type of cell–cell or cell–extracellular matrix signalling in multicellular organisms that requires close contact. In this type of signalling, a ligand on one surface binds to a receptor on another adjacent surface. Hence, this stands in contrast to releasing a signaling molecule by diffusion into extracellular space, the use of long-range conduits like membrane nanotubes and cytonemes (akin to 'bridges') or the use of extracellular vesicles like exosomes or microvesicles (akin to 'boats').
Dendritic cellA dendritic cell (DC) is an antigen-presenting cell (also known as an accessory cell) of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and adaptive immune systems. Dendritic cells are present in tissues that are in contact with the body's external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell), and the inner lining of the nose, lungs, stomach and intestines.
Gene expression profilingIn the field of molecular biology, gene expression profiling is the measurement of the activity (the expression) of thousands of genes at once, to create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a particular treatment. Many experiments of this sort measure an entire genome simultaneously, that is, every gene present in a particular cell. Several transcriptomics technologies can be used to generate the necessary data to analyse.
Cell cycleThe cell cycle, or cell-division cycle, is the series of events that take place in a cell that causes it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division. In cells with nuclei (eukaryotes, i.e., animal, plant, fungal, and protist cells), the cell cycle is divided into two main stages: interphase and the mitotic (M) phase (including mitosis and cytokinesis).
Genetically modified mouseA genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (Mus musculus) that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. Together with patient-derived xenografts (PDXs), GEMMs are the most common in vivo models in cancer research. Both approaches are considered complementary and may be used to recapitulate different aspects of disease.
