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)

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.

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.

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.

Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.

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.

Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.

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.

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)

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.

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.

A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.

An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.

Progenitor cells from which all blood cells derive.

Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.

An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.

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.

An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.

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.

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.

An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.

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)

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.

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.

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.

Disease having a short and relatively severe course.

The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.

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.

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.

Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.

A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.

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.

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.

A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.

Established cell cultures that have the potential to propagate indefinitely.

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)

Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.

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.

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 type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.

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.

A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.

A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.

A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.

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.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.

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.

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.

Mapping of the KARYOTYPE of a cell.

DNA present in neoplastic tissue.

A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain. Runx1 is frequently mutated in human LEUKEMIAS.

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.

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.

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.

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.

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 form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.

A cell line derived from cultured tumor cells.

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).

A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.

An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).

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 cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.

Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.

A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.

Antibodies produced by a single clone of cells.

Inbred AKR mice are a strain of laboratory mice that are homozygous at all gene loci and have a high incidence of developing certain diseases, such as leukemia and autoimmune disorders, making them useful for research purposes in biomedicine.

A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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.

White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).

Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.

A group of transmissible viral diseases of chickens and turkeys. Liver tumors are found in most forms, but tumors can be found elsewhere.

A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.

A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.

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.

Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.

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.

BENZOIC ACID amides.

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.

RNA present in neoplastic tissue.

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.

Piperazines are a class of heterocyclic organic compounds containing a seven-membered ring with two nitrogen atoms at positions 1 and 4, often used in pharmaceuticals as smooth muscle relaxants, antipsychotics, antidepressants, and antihistamines, but can also be found as recreational drugs with stimulant and entactogen properties.

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.

Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.

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).

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.

Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)

The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.

Phospholipids which have an alcohol moiety in ethereal linkage with a saturated or unsaturated aliphatic alcohol. They are usually derivatives of phosphoglycerols or phosphatidates. The other two alcohol groups of the glycerol backbone are usually in ester linkage. These compounds are widely distributed in animal tissues.

Nucleotides containing arabinose as their sugar moiety.

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 family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.

The action of a drug in promoting or enhancing the effectiveness of another drug.

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.

Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.

Experimental transplantation of neoplasms in laboratory animals for research purposes.

A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.

Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.

Therapeutic act or process that initiates a response to a complete or partial remission level.

A form of cutaneous T-cell lymphoma manifested by generalized exfoliative ERYTHRODERMA; PRURITUS; peripheral lymphadenopathy, and abnormal hyperchromatic mononuclear (cerebriform) cells in the skin, LYMPH NODES, and peripheral blood (Sezary cells).

Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.

Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.

Thymidine is a pyrimidine nucleoside, consisting of a thymine base linked to a deoxyribose sugar by a β-N1-glycosidic bond, which plays a crucial role in DNA replication and repair processes as one of the four nucleosides in DNA.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

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.

Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides.

A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.

The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.

A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.

Tetracyclic spiro-BENZAZEPINES isolated from the seeds of CEPHALOTAXUS. They are esters of the alkaloid cephalotaxine and may be effective as antineoplastic agents.

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.

A species of ALPHARETROVIRUS causing anemia in fowl.

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.

The parent cells that give rise to both cells of the GRANULOCYTE lineage and cells of the monocyte/macrophage lineage.

A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72.

An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.

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).

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.

The rate dynamics in chemical or physical systems.

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.

Polyacenes with four ortho-fused benzene rings in a straight linear arrangement. This group is best known for the subclass called TETRACYCLINES.

Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (= PLANT GROWTH REGULATORS).

An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 2.7.1.74.

Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.

The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.

The relationship between the dose of an administered drug and the response of the organism to the drug.

Inorganic or organic compounds that contain arsenic.

A general term for various neoplastic diseases of the lymphoid tissue.

A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.

Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.

A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.

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.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.

An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).

A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. EC 2.7.7.31.

Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)

A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.

Elements of limited time intervals, contributing to particular results or situations.

A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.

The short, acrocentric human chromosomes, called group G in the human chromosome classification. This group consists of chromosome pairs 21 and 22 and the Y chromosome.

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.

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.

A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.

Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.

Signal molecules that are involved in the control of cell growth and differentiation.

4-Hydroxy-1-(beta-D-ribofuranosyl)-2-pyridinone. Analog of uridine lacking a ring-nitrogen in the 3-position. Functions as an antineoplastic agent.

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.

Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.

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.

Proteins prepared by recombinant DNA technology.

A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) isolated from spontaneous leukemia in AKR strain mice.

Hydrolytic enzyme activity used as a histocytochemical test for the presence of esterases in tissue. Substrate used is 3-hydroxy-4'-nitro-2-naphthanilide chloroacetate (naphthol AS-D).

A spectrum of disorders characterized by clonal expansions of the peripheral blood LYMPHOCYTE populations known as large granular lymphocytes which contain abundant cytoplasm and azurophilic granules. Subtypes develop from either CD3-negative NATURAL KILLER CELLS or CD3-positive T-CELLS. The clinical course of both subtypes can vary from spontaneous regression to progressive, malignant disease.

The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.

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.

A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.

Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.

Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.

The return of a sign, symptom, or disease after a remission.

Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.

A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1.

Chronic refractory anemia with granulocytopenia, and/or thrombocytopenia. Myeloblasts and progranulocytes constitute 5 to 40 percent of the nucleated marrow cells.

Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.

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 introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.

Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.

Transplantation between animals of different species.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.

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.

Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.

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.

A myelodysplastic-myeloproliferative disease characterized by monocytosis, increased monocytes in the bone marrow, variable degrees of dysplasia, but an absence of immature granulocytes in the blood.

An encapsulated lymphatic organ through which venous blood filters.

Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.

Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.

A genus of soft-shell clams in the family Myidae, class BIVALVIA.

An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.

Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)

Infections caused by the HTLV or BLV deltaretroviruses. They include human T-cell leukemia-lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED).

Glycoproteins found on the membrane or surface of cells.

Antimetabolites that are useful in cancer chemotherapy.

A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.

Immunological rejection of leukemia cells following bone marrow transplantation.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.