Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20)
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.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
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)
A rare, aggressive variant of MULTIPLE MYELOMA characterized by the circulation of excessive PLASMA CELLS in the peripheral blood. It can be a primary manifestation of multiple myeloma or develop as a terminal complication during the disease.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
Removal of bone marrow and evaluation of its histologic picture.
The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.
Bone marrow diseases, also known as hematologic or blood disorders, refer to conditions that affect the production and function of blood cells within the bone marrow, such as leukemia, lymphoma, myeloma, and aplastic anemia, potentially leading to complications like anemia, neutropenia, thrombocytopenia, and increased susceptibility to infections or bleeding.
Neoplasms associated with a proliferation of a single clone of PLASMA CELLS and characterized by the secretion of PARAPROTEINS.
Neoplasms located in the bone marrow. They are differentiated from neoplasms composed of bone marrow cells, such as MULTIPLE MYELOMA. Most bone marrow neoplasms are metastatic.
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
Progenitor cells from which all blood cells derive.
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.
The residual portion of BLOOD that is left after removal of BLOOD CELLS by CENTRIFUGATION without prior BLOOD COAGULATION.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Bone loss due to osteoclastic activity.
Techniques for the removal of subpopulations of cells (usually residual tumor cells) from the bone marrow ex vivo before it is infused. The purging is achieved by a variety of agents including pharmacologic agents, biophysical agents (laser photoirradiation or radioisotopes) and immunologic agents. Bone marrow purging is used in both autologous and allogeneic BONE MARROW TRANSPLANTATION.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
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.
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).
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. These cells frequently secrete a structurally homogeneous immunoglobulin (M-component) and/or an abnormal immunoglobulin.
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.
Tumors or cancer located in bone tissue or specific BONES.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
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.
Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
Diseases of BONES.
The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.
Transplantation of an individual's own tissue from one site to another site.
An encapsulated lymphatic organ through which venous blood filters.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
A slow-growing benign pseudotumor in which plasma cells greatly outnumber the inflammatory cells.
Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.
Elements of limited time intervals, contributing to particular results or situations.
Irradiation of the whole body with ionizing or non-ionizing radiation. It is applicable to humans or animals but not to microorganisms.
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of "hairy" or "flagellated" cells in the blood and bone marrow.
Renewal or repair of lost bone tissue. It excludes BONY CALLUS formed after BONE FRACTURES but not yet replaced by hard bone.
An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.
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.
A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.
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.
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.
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
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.
A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.
Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.
Cell separation is the process of isolating and distinguishing specific cell types or individual cells from a heterogeneous mixture, often through the use of physical or biological techniques.
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.
Antibodies produced by a single clone of cells.
Disease having a short and relatively severe course.
The process of bone formation. Histogenesis of bone including ossification.
Therapeutic act or process that initiates a response to a complete or partial remission level.
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.
A syndecan that interacts with EXTRACELLULAR MATRIX PROTEINS and plays a role CELL PROLIFERATION and CELL MIGRATION.
Established cell cultures that have the potential to propagate indefinitely.
Leukemia L1210 is a designation for a specific murine (mouse) leukemia cell line that was originally isolated from a female mouse with an induced acute myeloid leukemia, which is widely used as a model in cancer research, particularly for in vivo studies of drug efficacy and resistance.
Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A general term for various neoplastic diseases of the lymphoid tissue.
The grafting of bone from a donor site to a recipient site.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.
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 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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
A species of GAMMARETROVIRUS causing leukemia, lymphosarcoma, immune deficiency, or other degenerative diseases in cats. Several cellular oncogenes confer on FeLV the ability to induce sarcomas (see also SARCOMA VIRUSES, FELINE).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.
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.
Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
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)
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets.
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.
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.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
A classification of B-lymphocytes based on structurally or functionally different populations of cells.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
The type species of DELTARETROVIRUS that causes a form of bovine lymphosarcoma (ENZOOTIC BOVINE LEUKOSIS) or persistent lymphocytosis.
A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Mapping of the KARYOTYPE of a cell.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The return of a sign, symptom, or disease after a remission.
Conditions characterized by the presence of M protein (Monoclonal protein) in serum or urine without clinical manifestations of plasma cell dyscrasia.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
Synthetic or natural materials for the replacement of bones or bone tissue. They include hard tissue replacement polymers, natural coral, hydroxyapatite, beta-tricalcium phosphate, and various other biomaterials. The bone substitutes as inert materials can be incorporated into surrounding tissue or gradually replaced by original tissue.
Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)
Metabolic bone diseases are a group of disorders that affect the bones' structure and strength, caused by disturbances in the normal metabolic processes involved in bone formation, resorption, or mineralization, including conditions like osteoporosis, osteomalacia, Paget's disease, and renal osteodystrophy.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
Proteins prepared by recombinant DNA technology.
The longest and largest bone of the skeleton, it is situated between the hip and the knee.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
The relationship between the dose of an administered drug and the response of the organism to the drug.
An individual that contains cell populations derived from different zygotes.
Glycoproteins found on the membrane or surface of cells.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Breaks in bones.
The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
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.
A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A cell line derived from cultured tumor cells.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
An acute myeloid leukemia in which 20-30% of the bone marrow or peripheral blood cells are of megakaryocyte lineage. MYELOFIBROSIS or increased bone marrow RETICULIN is common.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
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.
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.
Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.
Individuals supplying living tissue, organs, cells, blood or blood components for transfer or transplantation to histocompatible recipients.
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.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
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.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.
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.
An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.
The initial phase of chronic myeloid leukemia consisting of an relatively indolent period lasting from 4 to 7 years. Patients range from asymptomatic to those exhibiting ANEMIA; SPLENOMEGALY; and increased cell turnover. There are 5% or fewer blast cells in the blood and bone marrow in this phase.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
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.
Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.
Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include INTERLEUKIN-3; (IL-3); GRANULOCYTE COLONY-STIMULATING FACTOR; (G-CSF); MACROPHAGE COLONY-STIMULATING FACTOR; (M-CSF); and GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; (GM-CSF).
Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
A lymphoproliferative disorder characterized by pleomorphic B-LYMPHOCYTES including PLASMA CELLS, with increased levels of monoclonal serum IMMUNOGLOBULIN M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include ANEMIA; HEMORRHAGES; and hyperviscosity.
Inbred C3H mice are a strain of laboratory mice that have been selectively bred to maintain a high degree of genetic uniformity and share specific genetic characteristics, including susceptibility to certain diseases, which makes them valuable for biomedical research purposes.
Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept.
A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the PHARYNX. There is one on each side of the oropharynx in the fauces between the anterior and posterior pillars of the SOFT PALATE.