Leukemia, Myelomonocytic, Chronic: 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.Leukemia, Myelomonocytic, Acute: A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.Leukemia, Myelomonocytic, Juvenile: A leukemia affecting young children characterized by SPLENOMEGALY, enlarged lymph nodes, rashes, and hemorrhages. Traditionally classed as a myeloproliferative disease, it is now considered a mixed myeloproliferative-mylelodysplastic disorder.Leukemia: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)Leukemia, Myeloid, Acute: 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.Leukemia, Experimental: Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.Leukemia, Lymphocytic, Chronic, B-Cell: 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, Lymphoid: Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.Leukemia, Monocytic, Acute: An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: 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 Virus, Murine: 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.Precursor Cell Lymphoblastic Leukemia-Lymphoma: A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.Oncogene Proteins v-myb: Transforming proteins coded by myb oncogenes. Transformation of cells by v-myb in conjunction with v-ets is seen in the avian E26 leukemia virus.Leukemia, Myeloid: 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.Gene Expression Regulation, Leukemic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.Leukemia, T-Cell: A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Monocytes: 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.Moloney murine leukemia virus: 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.Myeloproliferative Disorders: 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.Myeloid-Lymphoid Leukemia Protein: 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.HL-60 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)Antigens, Differentiation, Myelomonocytic: 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.Leukemia, Hairy Cell: 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.Myelodysplastic Syndromes: 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.Leukemia L1210Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Leukemia, B-Cell: A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Karyotyping: Mapping of the KARYOTYPE of a cell.Leukemia Virus, Bovine: The type species of DELTARETROVIRUS that causes a form of bovine lymphosarcoma (ENZOOTIC BOVINE LEUKOSIS) or persistent lymphocytosis.Leukemia Virus, Feline: 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).Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Friend murine leukemia virus: 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.Leukemia, Radiation-Induced: Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.Cytarabine: 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)Acute Disease: Disease having a short and relatively severe course.Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.Leukemia P388: An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.Leukemia, Biphenotypic, Acute: An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level.Cell Transformation, Neoplastic: 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.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.fms-Like Tyrosine Kinase 3: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Preleukemia: 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.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Core Binding Factor Alpha 2 Subunit: 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.Leukemia-Lymphoma, Adult T-Cell: Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.Immunophenotyping: 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.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative: A myelodysplastic/myeloproliferative disorder characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to CHRONIC MYELOID LEUKEMIA, but cytogenetically lacking a PHILADELPHIA CHROMOSOME or bcr/abl fusion gene (GENES, ABL).Proto-Oncogene Proteins: 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.Neoplasm Proteins: 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.Proto-Oncogenes: 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.Leukemia, Megakaryoblastic, Acute: 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.Myelodysplastic-Myeloproliferative Diseases: Clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either MYELODYSPLASTIC SYNDROMES or MYELOPROLIFERATIVE DISORDERS.AKR murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) isolated from spontaneous leukemia in AKR strain mice.Retroviridae Proteins, Oncogenic: Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.Myeloid Progenitor Cells: Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.Avian myeloblastosis virus: A species of ALPHARETROVIRUS causing anemia in fowl.Fusion Proteins, bcr-abl: 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.Myeloid Cells: The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).Leukemia, Myeloid, Chronic-Phase: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Granulocyte Precursor Cells: The cells in the granulocytic series that give rise to mature granulocytes (NEUTROPHILS; EOSINOPHILS; and BASOPHILS). These precursor cells include myeloblasts, promyelocytes, myelocytes and metamyelocytes.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Prognosis: 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.Anemia, Refractory: A severe sometimes chronic anemia, usually macrocytic in type, that does not respond to ordinary antianemic therapy.Antigens, Surface: 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.Precursor B-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.Abelson murine leukemia virus: A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Granulocyte-Macrophage Colony-Stimulating Factor: 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.U937 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.Chromosome Inversion: An aberration in which a chromosomal segment is deleted and reinserted in the same place but turned 180 degrees from its original orientation, so that the gene sequence for the segment is reversed with respect to that of the rest of the chromosome.Chromosomes, Human, Pair 16: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Oncogenes: 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.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Neurofibromin 1: A protein found most abundantly in the nervous system. Defects or deficiencies in this protein are associated with NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome. Mutations in the gene (GENE, NEUROFIBROMATOSIS 1) affect two known functions: regulation of ras-GTPase and tumor suppression.Bone Marrow Transplantation: 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.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Hematopoiesis: The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Retroviridae: 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).Apoptosis: 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.Chromosomes, Human, 16-18: The short, submetacentric human chromosomes, called group E in the human chromosome classification. This group consists of chromosome pairs 16, 17, and 18.Tretinoin: 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).Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Chromosomes, Human, Pair 11: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Leukemia, Plasma Cell: 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.Leukemia, Myeloid, Accelerated Phase: The phase of chronic myeloid leukemia following the chronic phase (LEUKEMIA, MYELOID, CHRONIC-PHASE), where there are increased systemic symptoms, worsening cytopenias, and refractory LEUKOCYTOSIS.Genes, myb: Retrovirus-associated DNA sequences (v-myb) originally isolated from the avian myeloblastosis and E26 leukemia viruses. The proto-oncogene c-myb codes for a nuclear protein involved in transcriptional regulation and appears to be essential for hematopoietic cell proliferation. The human myb gene is located at 6q22-23 on the short arm of chromosome 6. This is the point of break in translocations involved in T-cell acute lymphatic leukemia and in some ovarian cancers and melanomas. (From Ibelgaufts, Dictionary of Cytokines, 1995).K562 Cells: An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.Patient Outcome AssessmentBone Marrow Examination: Removal of bone marrow and evaluation of its histologic picture.Cytogenetics: A subdiscipline of genetics which deals with the cytological and molecular analysis of the CHROMOSOMES, and location of the GENES on chromosomes, and the movements of chromosomes during the CELL CYCLE.Sialic Acid Binding Ig-like Lectin 3: 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, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.RNA, Neoplasm: RNA present in neoplastic tissue.Macrophages: 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.)Leukemia, Prolymphocytic, T-Cell: 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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Polymerase Chain Reaction: 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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Antineoplastic Combined Chemotherapy Protocols: 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.Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Dimethyl Sulfoxide: 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.B-Lymphocytes: 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.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Human T-lymphotropic virus 1: A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).Leukemia, Prolymphocytic: 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.Growth Inhibitors: 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).Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.Treatment Outcome: 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.Colony-Forming Units Assay: A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.DNA, Neoplasm: DNA present in neoplastic tissue.Recurrence: The return of a sign, symptom, or disease after a remission.Antigens, Neoplasm: 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.Precursor T-Cell Lymphoblastic Leukemia-Lymphoma: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Chromosome Disorders: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)Cell Line, Tumor: A cell line derived from cultured tumor cells.Leukemia, Basophilic, Acute: A rare acute myeloid leukemia in which the primary differentiation is to BASOPHILS. It is characterized by an extreme increase of immature basophilic granulated cells in the bone marrow and blood. Mature basophils are usually sparse.Leukemic Infiltration: 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.Transfection: 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.Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 188.8.131.52.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Blood Cells: The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.Chromosomes, Human, 19-20: The short, metacentric human chromosomes, called group F in the human chromosome classification. This group consists of chromosome pairs 19 and 20.Interleukin-3: 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.Naphthol AS D Esterase: 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).Philadelphia Chromosome: 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).Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.In Situ Hybridization, Fluorescence: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Chromosomes, Human, Pair 8: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Graft vs Leukemia Effect: Immunological rejection of leukemia cells following bone marrow transplantation.Chromosome Banding: Staining of bands, or chromosome segments, allowing the precise identification of individual chromosomes or parts of chromosomes. Applications include the determination of chromosome rearrangements in malformation syndromes and cancer, the chemistry of chromosome segments, chromosome changes during evolution, and, in conjunction with cell hybridization studies, chromosome mapping.Chromosomes, Human, Pair 7: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Fatal Outcome: 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.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 184.108.40.206.Antimetabolites, Antineoplastic: Antimetabolites that are useful in cancer chemotherapy.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Leukemia Inhibitory Factor Receptor alpha Subunit: A receptor subunit that combines with CYTOKINE RECEPTOR GP130 to form the dual specificity receptor for LEUKEMIA INHIBITORY FACTOR and ONCOSTATIN M. The subunit is also a component of the CILIARY NEUROTROPHIC FACTOR RECEPTOR. Both membrane-bound and secreted isoforms of the receptor subunit exist due to ALTERNATIVE SPLICING of its mRNA. The secreted isoform is believed to act as an inhibitory receptor, while the membrane-bound form is a signaling receptor.Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell.Colony-Stimulating Factors: 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).Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Hematopoietic Stem Cell Transplantation: 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.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Janus Kinase 2: A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Genes, Intracisternal A-Particle: Genes of IAP elements (a family of retrovirus-like genetic elements) which code for virus-like particles (IAPs) found regularly in rodent early embryos. ("Intracisternal" refers to the cisternae of the endoplasmic reticulum.) Under certain circumstances, such as DNA hypomethylation they are transcribed. Their transcripts are found in a variety of neoplasms, including plasmacytomas, neuroblastoma, rhabdomyosarcomas, teratocarcinomas, and colon carcinomas.Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: Receptors that bind and internalize the granulocyte-macrophage stimulating factor. Their MW is believed to be 84 kD. The most mature myelomonocytic cells, specifically human neutrophils, macrophages, and eosinophils, express the highest number of affinity receptors for this growth factor.Neoplasm, Residual: Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Proto-Oncogene Proteins c-myb: Cellular DNA-binding proteins encoded by the myb gene (GENES, MYB). They are expressed in a wide variety of cells including thymocytes and lymphocytes, and regulate cell differentiation. Overexpression of myb is associated with autoimmune diseases and malignancies.Proto-Oncogene Proteins c-hck: Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.Proviruses: Duplex DNA sequences in eukaryotic chromosomes, corresponding to the genome of a virus, that are transmitted from one cell generation to the next without causing lysis of the host. Proviruses are often associated with neoplastic cell transformation and are key features of retrovirus biology.Leukemia, Large Granular Lymphocytic: 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.Cytogenetic Analysis: Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.Survival Analysis: 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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Proto-Oncogene Proteins c-cbl: Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Protein Tyrosine Phosphatase, Non-Receptor Type 11: A subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.Scleromyxedema: A connective tissue disorder characterized by widespread thickening of SKIN with a cobblestone-like appearance. It is caused by proliferation of FIBROBLASTS and deposition of MUCIN in the DERMIS in the absence of thyroid disease. Most scleromyxedema cases are associated with a MONOCLONAL GAMMOPATHY, immunoglobulin IgG-lambda.Megakaryocytes: Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Mice, Inbred C57BLLeukopoiesis: The process of generating white blood cells (LEUKOCYTES) from the pluripotent HEMATOPOIETIC STEM CELLS of the BONE MARROW. There are two significant pathways to generate various types of leukocytes: MYELOPOIESIS, in which leukocytes in the blood are derived from MYELOID STEM CELLS, and LYMPHOPOIESIS, in which leukocytes of the lymphatic system (LYMPHOCYTES) are generated from lymphoid stem cells.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Avian leukosis virus: The type species of ALPHARETROVIRUS producing latent or manifest lymphoid leukosis in fowl.Receptor, Macrophage Colony-Stimulating Factor: A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Retroviridae Infections: Virus diseases caused by the RETROVIRIDAE.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Oxides: 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.Lymphocytes: 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.Gene Products, tax: Transcriptional trans-acting proteins of the promoter elements found in the long terminal repeats (LTR) of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The tax (trans-activator x; x is undefined) proteins act by binding to enhancer elements in the LTR.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Cell Transformation, Viral: An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.Antigens, CD11: A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Proto-Oncogene Proteins c-ets: A family of transcription factors that share a unique DNA-binding domain. The name derives from viral oncogene-derived protein oncogene protein v-ets of the AVIAN ERYTHROBLASTOSIS VIRUS.Blotting, Southern: 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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Arsenicals: Inorganic or organic compounds that contain arsenic.Idarubicin: An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Myelomonocyte: A myelomonocyte is a type of cell observed in chronic myelomonocytic leukemia. It bears a resemblance to both a myelocyte and monocyte.Childhood leukemia: Childhood leukemia is a type of leukemia, usually acute lymphocytic leukemia (ALL), and a type of childhood cancer. The cure rate of childhood leukemia is generally higher than adult leukemia, approaching 90%, although some side effects of treatment last into adulthood.Minimally differentiated acute myeloblastic leukemiaB-cell chronic lymphocytic leukemiaMonocytic leukemiaMyeloid leukemiaBone marrow suppression: Bone marrow suppression or myelotoxicity (adjective myelotoxic) or myelosuppression is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine.Gammaretrovirus core encapsidation signalMyelodysplastic–myeloproliferative diseases: Myelodysplastic–myeloproliferative diseases are a category of hematological malignancies disorders created by the World Health Organization which have characteristics of both myelodysplastic and myeloproliferative conditions.Hairy cell leukemiaRefractory cytopenia with multilineage dysplasiaMyeloid: The term myeloid (myelogenous) is an adjective that can refer to a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets. Myeloid can be distinguished from the lymphoid progenitor cells that give rise to B cells and T cells.Pre-B-cell leukemia homeobox: Pre-B-cell leukemia homeobox (PBX) refers to a family of transcription factors.Bovine leukemia virus: Leucosis}}Reuben Rickard: Reuben Rickard (August 20, 1841 – February 28, 1896) was a mining engineer who served as President of the Town Board of Trustees in Berkeley, California from 1891 to 1893, and again for about one month during 1895.CytarabineGranulocyte: framed|Eosinophilic granulocyteColes PhillipsSymmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.CrenolanibAntileukemic drug: Antileukemic drugs, anticancer drugs that are used to treat one or more types of leukemia, include:Flow cytometry: In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.Adult T-cell leukemia/lymphomaImmunophenotyping: Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose.Genetic imbalance: Genetic imbalance is to describe situation when the genome of a cell or organism has more copies of some genes than other genes due to chromosomal rearrangements or aneuploidy.MinC: The MinC protein is one of three proteins encoded by the minB operon and which is required to generate pole to pole oscillations prior to bacterial cell division as a means of specifying the midzone of the cell. This function is achieved by preventing the formation of the divisome Z-ring around the poles.MyeloblastMature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Abelson: Abelson, originating from both Swedish and Yiddish, and derived from the name Abel, is the surname of:Monoclonal antibody therapyWorld Lymphoma Awareness Day: World Lymphoma Awareness Day (WLAD) is held on September 15 every year and is a day dedicated to raising awareness of lymphoma, an increasingly common form of cancer. It is a global initiative hosted by the Lymphoma Coalition (LC), a non-profit network organisation of 63 lymphoma patient groups from 44 countries around the world.Stem cell theory of aging: The stem cell theory of aging is a new theory which was formulated by several scientists and which postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue's (or organ's) original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age.DNA-binding proteinGranulocyte macrophage colony-stimulating factorJohn Payne ToddCD36 antigen: CD36 antigen is a transmembrane, highly glycosylated, glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. CD36 recognises oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin and Plasmodium falciparum infected erythrocytes.Neurofibromin 1: Neurofibromin 1 also known as neurofibromatosis-related protein NF-1 is a protein that in humans is encoded by the NF1 gene. Mutations in the NF1 gene are associated with neurofibromatosis type I (also known as von Recklinghausen disease) and Watson syndrome.Bone Marrow Transplantation (journal): Bone Marrow Transplantation is a peer-reviewed medical journal covering transplantation of bone marrow in humans. It is published monthly by the Nature Publishing Group.Pituitary-specific positive transcription factor 1: POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone.TretinoinDaunorubicinChromothripsis: Chromothripsis is the phenomenon by which up to thousands of clustered chromosomal rearrangements occur in a single event in localised and confined genomic regions in one or a few chromosomes, and is known to be involved in both cancer and congenital diseases. It occurs through one massive genomic rearrangement during a single catastrophic event in the cell's history.Plasma cell leukemia
(1/181) Transforming properties of the Huntingtin interacting protein 1/ platelet-derived growth factor beta receptor fusion protein.
We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor beta receptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFbetaR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3-independent growth. A kinase-inactive mutant is neither tyrosine-phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFbetaR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFbetaR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr --> Phe mutants of HIP1/PDGFbetaR in the known PDGFbetaR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFbetaR Tyr --> Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFbetaR. (+info)
(2/181) Study of p53 in elderly patients with myelodysplastic syndromes by immunohistochemistry and DNA analysis.
We analyzed the tumor suppressor gene product, p53, in elderly patients with myelodysplastic syndromes (MDS) and in overt leukemia patients after transformation from MDS using immunohistochemical techniques. We examined 52 MDS patients (mean age 79 years, range 68 to 96) from the time of initial diagnosis to death or development of overt leukemia. p53 protein was detected by immunohistochemistry (IHC) in 8/52 patients (15%) at initial diagnosis: 1/26 with refractory anemia (RA), 0/4 with RA with ringed sideroblasts, 3/11 with RA with an excess of blasts (RAEB), 3/8 with RAEB in transformation, and 1/3 with chronic myelomonocytic leukemia. We also analyzed gene mutations in patients with positive IHC. p53 mutations were detected in 3/8 (38%) patients. IHC-positive patients had a significantly higher incidence of leukemic transformation and the presence of a complex karyotype with monosomy 17. IHC-positive cells included blasts as well as mature myeloid cells, erythroblasts, and megakaryocytes. Scrutiny of our data in combination with previous data revealed that patients with positive IHC in multilineage cells were older than those in whom positivity was noted mostly in myeloblasts. This suggests that p53 IHC positivity with a multilineage pattern may be a characteristic of MDS in older patients. (+info)
(3/181) Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia.
PURPOSE: To evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Fifty-nine patients with MDSs and 27 with CMML were enrolled. They were either previously untreated (66%) or had received only biologic agents (14%) or chemotherapy with or without biologic agents (20%). Treatment consisted of topotecan 1.25 mg/m(2) by continuous intravenous infusion daily for 5 days and cytarabine 1. 0 g/m(2) by infusion over 2 hours daily for 5 days. Prophylaxis included antibacterial, antifungal, and antiviral agents. At a median follow-up of 7 months, all 86 patients were assessable for response and toxicity. RESULTS: Complete remission (CR) was observed in 48 patients (56%; 61% with MDSs, 44% with CMML; P =.15). Similar CR rates were observed for patients with good-risk and poor-risk MDS (70% and 56%, respectively). The treatment effectively induced CR in patients with a poor-prognosis karyotype involving chromosomes 5 and 7 (CR, 71%) and secondary MDSs (CR, 72%). Fifty-four patients received one induction course, 25 patients received two, and the rest received more than two. The median number of continuation courses was two. The median overall duration of CR was 34 weeks (50 weeks for MDSs and 33 weeks for CMML). The median survival was 60 weeks for MDS and 44 weeks for CMML patients. CR and survival durations were longer in patients with refractory anemia with excess blasts (RAEB). Grade 3 or 4 mucositis or diarrhea was observed in three patients each. Fever was observed in 63%, and infections in 49% of patients. Six patients (7%) died during induction therapy. CONCLUSION: Topotecan and cytarabine induced high CR rates in unselected patients with MDSs and CMML, particularly among patients with poor-prognosis cytogenetics and secondary MDSs. Topotecan-cytarabine is an active induction regimen in MDS and CMML patients, is well tolerated, and is associated with a low mortality rate. (+info)
(4/181) Characterization of the chronic myelomonocytic leukemia associated TEL-PDGF beta R fusion protein.
The t(5;12) translocation, associated with chronic myelomonocytic leukemia, generates a novel gene encoding a protein, TEL-PDGF beta R, composed of the 154 amino-terminal amino acids of the transcription factor TEL and the transmembrane and intracellular part of the PDGF beta-receptor (PDGF beta R). TEL also occurs as a tumor-associated fusion partner for the tyrosine kinases c-ABL, JAK2 and TRK-C. Previous studies have demonstrated growth promoting activity of TEL-PDGF beta R and also indicated that the TEL moiety activates the tyrosine kinase of the PDGF beta R through the formation of TEL-PDGF beta R oligomers. We demonstrate that tyrosine phosphorylation of the fusion protein can be attenuated through overexpression of the TEL part of TEL-PDGF beta R, suggesting a strategy for antagonizing the signaling of TEL-PDGF beta R, and other TEL-fusion proteins containing tyrosine kinase domains. Comparison of BaF/3 cell lines expressing TEL-PDGF beta R and ligand-stimulated PDGF beta R revealed that only TEL-PDGF beta R expression conferred IL-3-independent growth, suggesting differences in signaling capacity of the two proteins. Finally, tyrosine residues 17 and 27 in TEL-PDGF beta R was identified as autophosphorylation sites in TEL-PDGF beta R. (+info)
(5/181) Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors.
Juvenile myelomonocytic leukemia (JMML) is an early childhood disease for which there is no effective therapy. Therapy with 13-cis retinoic acid or low-dose chemotherapy can induce some responses, but neither mode is curative. Stem cell transplantation can produce lasting remissions but is hampered by high rates of relapse. The pathogenesis of JMML involves deregulated cytokine signal transduction through the Ras signaling pathway, with resultant selective hypersensitivity of JMML cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). A JMML mouse model, achieved through homozygous deletion of the neurofibromatosis gene, confirmed the involvement of deregulated Ras in JMML pathogenesis. With this pathogenetic knowledge, mechanism-based treatments are now being developed and tested. Ras is critically dependent on a prenylation reaction for its signal transduction abilities. Farnesyltransferase inhibitors are compounds that were developed specifically to block the prenylation of Ras. Two of these compounds, L-739,749 and L-744, 832, were tested for their ability to inhibit spontaneous JMML granulocyte-macrophage colony growth. Within a dose range of 1 to 10 micromol/L, each compound demonstrated dose-dependent inhibition of JMML colony growth. An age-matched patient with a different disease and GM-CSF-stimulated normal adult marrow cells also demonstrated dose-dependent inhibitory effects on colony growth, but they were far less sensitive to these compounds than JMML hematopoietic progenitors. Even if the addition of L-739,749 were delayed for 5 days, significant inhibitory effects would still show in JMML cultures. These results demonstrate that a putative Ras-blocking compound can have significant growth inhibitory effects in vitro, perhaps indicating a potential treatment for JMML. (Blood. 2000;95:639-645) (+info)
(6/181) Regulation of drug sensitivity by ribosomal protein S3a.
When bcl-2 is immunoprecipitated from (32)P-labeled cell extracts of all-trans retinoic acid (ATRA)-treated acute myeloblastic leukemia (AML) blasts, a phosphorylated protein of approximately 30 kd is coprecipitated. This protein has been identified as ribosomal protein S3a. The biologic effects of S3a include favoring apoptosis and enhancing the malignant phenotype. We sought to determine whether S3a, like bcl-2, influenced the response of cells to chemotherapeutic drugs and ATRA. Cell lines were studied in which S3a was genetically increased or disrupted; increased S3a was regularly associated with increased plating efficiency and increased sensitivity to either cytosine arabinoside (ara-C) or doxorubicin (DNR). S3a did not affect the sensitivity of cells to paclitaxel. Pulse exposures to either (3)HTdR or ara-C showed a greater percentage of clonogenic cells in the S phase of the cell cycle in cells with increased S3a than in controls. Cells with increased S3a responded to ATRA by increased ara-C or DNR sensitivity, whereas cells with reduced S3a protein were either protected by ATRA or not affected. We studied cryopreserved blast cells from patients with AML or chronic myelomonocytic leukemia (CMML). S3a protein levels were heterogeneous in these populations. In 32 cryopreserved blast populations, S3a levels were significantly correlated with both bcl-2 and with cell growth in culture. As in cell lines, high S3a in cryopreserved blasts was associated with ATRA-induced sensitization to ara-C. No significant association was seen between S3a levels and response to treatment. (+info)
(7/181) Nf1 and Gmcsf interact in myeloid leukemogenesis.
The NF1 tumor suppressor gene encodes neurofibromin, a GTPase-activating protein (GAP) for p21ras (Ras). Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML). Some heterozygous Nf1 mutant mice develop a similar myeloproliferative disorder (MPD), and adoptive transfer of Nf1-deficient fetal liver cells consistently induces this MPD. Human JMML and murine Nf1-deficient cells are hypersensitive to granulocyte-macrophage colony-stimulating factor (GM-CSF) in methylcellulose cultures. We generated hematopoietic cells deficient in both Nf1 and Gmcsf to test whether GM-CSF is required to drive excessive proliferation of Nf1-/- cells in vivo. Here we show that GM-CSF play a central role in establishing and maintaining the MPD and that recipients engrafted with Nf1-/- Gmcsf-/- hematopoietic cells are hypersensitive to exogenous GM-CSF. (+info)
(8/181) Chronic myelomonocytic leukemia in a cat.
A 1-year-old spayed domestic short-haired cat was referred with anorexia and weight loss. Hematologic findings indicated nonregenerative anemia, severe neutropenia and monocytosis. The feline leukemia virus (FeLV) antigen test was positive reaction by enzyme-linked immunosorbent assay. Dysgranulopoiesis with slight increase in blast cells were observed in bone marrow smears. On the basis of blood and bone marrow findings, the cat was diagnosed as chronic myelomonocytic leukemia (CMMoL), which possibly corresponds to a kind of the subtypes in human myelodysplastic syndrome (MDS). (+info)