glycogen and Leukemia--Myeloid

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Marrow Cells; Chromosomes, Human, 21-22 and Y; Chronic Disease; Cytoplasmic Granules; Genes; Genes, Regulator; Glycogen; Humans; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Microscopy, Electron; Phagocytosis; Spleen

Topics: Age Factors; Alkaline Phosphatase; Aminosalicylic Acids; Cell Differentiation; Child; Child, Preschool; Diagnosis, Differential; Esterases; Glycogen; Histocytochemistry; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Peroxidases; Phospholipids

Topics: Esterases; Exudates and Transudates; Fluorides; Glucocorticoids; Glycogen; Histocytochemistry; Humans; Hydrolases; Leukemia, Myeloid; Macrophages; Monocytes; Naphthaleneacetic Acids; Oxidoreductases; Skin Window Technique; Sodium; Staining and Labeling

The rapid proliferation of myeloid leukemia cells is highly dependent on increased glucose metabolism. Through an unbiased metabolomics analysis of leukemia cells, we found that the glycogenic precursor UDP-D-glucose is pervasively upregulated, despite low glycogen levels. Targeting the rate-limiting glycogen synthase 1 (GYS1) not only decreased glycolytic flux but also increased activation of the glycogen-responsive AMP kinase (AMPK), leading to significant growth suppression. Further, genetic and pharmacological hyper-activation of AMPK was sufficient to induce the changes observed with GYS1 targeting. Cancer genomics data also indicate that elevated levels of the glycogenic enzymes GYS1/2 or GBE1 (glycogen branching enzyme 1) are associated with poor survival in AML. These results suggest a novel mechanism whereby leukemic cells sustain aberrant proliferation by suppressing excess AMPK activity through elevated glycogenic flux and provide a therapeutic entry point for targeting leukemia cell metabolism.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Case-Control Studies; Cell Proliferation; Flow Cytometry; Glycogen; Glycogen Synthase; Glycolysis; HEK293 Cells; Humans; Leukemia, Myeloid; Metabolomics; Mice; Phosphorylation; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Survival Rate; Tumor Cells, Cultured

Periodate-reactive glycoconjugates in human leukaemic cells were examined electron microscopically by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method. Granules in ALL cells were classified into 4 types based on PA-TCH-SP staining features. Abnormal granules containing glycogen were observed only in children with treatment-resistant ALL. Cytoplasmic granules in leukaemic cells of patients with AML and acute monocytic leukaemia exhibited moderate reactivity. The distribution pattern of glycogen in the cytoplasm of leukaemic cells was classified into 3 types, one lacking glycogen, one containing small glycogen particles scattered throughout cytoplasm, and one showing clusters of glycogen particles. Cells with glycogen clusters were observed in ALL cells and in erythroblasts from patients with erythroleukaemia. PA-TCH-SP reactivity was detected in the rough endoplasmic reticulum in acute promyelocytic leukaemia but not in ALL or other types of AML. Megakaryoblasts in megakaryocytic crisis of chronic myelogenous leukaemia exhibited characteristic PA-TCH-SP reactivity similar to that of normal megakaryocytes.

Topics: Bone Marrow; Cytoplasmic Granules; Glycogen; Humans; Indicators and Reagents; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Microscopy, Electron

We examined the fine structural distribution of glycogen particles in the cells of the erythrocyte series from thirty individuals with or without hematological disorders using the periodic acid-thiocarbo hydrazide-silver proteinate (PA-TCH-SP) technique, which is known to extend PAS staining to the ultrastructural level. In diseases exhibiting dyserythropoiesis, such as refractory anemia with excess of blasts (RAEB) and juvenile chronic myelocytic leukemia (JCML), glycogen particles remarkably increased. In diseases showing hypererythropoiesis such as iron deficiency anemia, hemolytic anemia, or in cells obtained from very small premature infants, an increase in glycogen particles was observed in most cases. Compared to the PAS staining technique, which also utilizes the periodic acid reaction, the PA-TCH-SP technique appears to be more sensitive for visualizing glycogen particles in PAS negative cells, in addition to its capability of demonstrating the distribution of periodate reactive substance at the fine structural level.

Topics: Anemia, Hypochromic; Erythrocytes; Female; Glycogen; Humans; Hydrazines; Infant, Newborn; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Male; Neoplastic Stem Cells; Periodic Acid-Schiff Reaction; Silver Proteins

Topics: Bone Marrow; Bone Marrow Cells; Enzyme Activation; Glycogen; Histocytochemistry; Humans; Leukemia, Myeloid; Leukocytes; Lipid Metabolism; Naphthol AS D Esterase; Peroxidases

Topics: Alkaline Phosphatase; DNA; Glycogen; Histocytochemistry; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Lipids; Megakaryocytes; Peroxidases; RNA

Topics: Blood Platelets; Glycogen; Humans; Leukemia, Hairy Cell; Leukemia, Myeloid; Lymphocytes

Topics: Anemia, Aplastic; Basophils; Blood Platelet Disorders; Blood Platelets; Bone Marrow; Bone Marrow Cells; Cell Membrane; Cytoplasmic Granules; Endoplasmic Reticulum; Eosinophils; Glycogen; Hematologic Diseases; Humans; Leukemia, Myeloid; Megakaryocytes; Microscopy, Electron; Mitochondria; Neutrophils; Peroxidases; Polyribosomes; Staining and Labeling; Syndrome; Vacuoles

Light and electron microscopic studies of platelets from 16 patients with myelomonocytic leukemia or "preleukemia" revealed major morphologic alterations in 15 and minor ones in 1. Although variable in severity from case to case, the changes present followed a distinct pattern. In most cases there were two platelet populations, one morphologically normal and one morpholigically abnormal. The most salient changes pertained to size (giant forms), shape (the platelets being rounded and probably spheroidal), decrease or absence of the microtubules, and increase in immature elements. A striking feature was the variation in size and shape of the granules, with truly giant forms (up to 2.5 mum) being present. In cytogenetic studies in 14 cases, there was no correlation between the chromosomal changes and the various types of platelet anomalies.

Topics: Adult; Aged; Agranulocytosis; Anemia, Aplastic; Blood Platelet Disorders; Blood Platelets; Bone Marrow; Bone Marrow Cells; Chromosome Aberrations; Chromosome Disorders; Endoplasmic Reticulum; Female; Glycogen; Humans; Leukemia, Myeloid; Male; Megakaryocytes; Microtubules; Middle Aged; Mitosis; Vacuoles

Topics: Acid Phosphatase; Adsorption; Alkaline Phosphatase; Animals; Animals, Newborn; Antibody Specificity; Blood Proteins; Bone Marrow; Bone Marrow Cells; Cell Line; Cells, Cultured; Cricetinae; Diploidy; Erythrocytes; Esterases; Glycogen; Humans; Immune Sera; Immunodiffusion; Karyotyping; Leukemia, Myeloid; Leukocytes; Lipids; Naphthalenes; Neoplasm Transplantation; Peroxidases; Rabbits

Topics: Adult; Aged; Blood Cell Count; Blood Glucose; Blood Platelets; Blood Proteins; Carbon Dioxide; Carbon Isotopes; Female; Glycogen; Humans; Lactates; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Methods; Middle Aged; Purpura, Thrombocytopenic; Remission, Spontaneous; Thrombin; Thrombocytopenia

Topics: Adult; Blood Cell Count; Blood Platelets; Female; Glycogen; Humans; Leukemia, Myeloid; Male; Megakaryocytes; Middle Aged

Topics: Adenosine; Adenosine Diphosphate; Blood Platelet Disorders; Blood Platelets; Blood Proteins; Cell Survival; Centrifugation, Density Gradient; Epinephrine; Glutamates; Glycogen; Glycogen Synthase; Histocompatibility Antigens; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lysine; Platelet Adhesiveness; Prostaglandins; Purpura, Thrombocytopenic; Thrombin; Thrombocytopenia

Topics: Aged; Eosinophilia; Erythrocytes; Female; Galactose; Genes; Glycogen; Humans; Karyotyping; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Lymphocytes; Male; Nucleotidyltransferases; Statistics as Topic; Trisomy; Uracil Nucleotides

Topics: Adult; Aged; Busulfan; Glucose; Glycogen; Histocytochemistry; Humans; Leukemia, Myeloid; Middle Aged; Neutrophils; Polycythemia Vera; Tritium

Topics: Blood Platelets; Diabetes Mellitus; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Liver Cirrhosis; Microscopy, Phase-Contrast; Myeloproliferative Disorders; Polycythemia; Primary Myelofibrosis; Purpura, Thrombocytopenic; Remission, Spontaneous; Uremia; von Willebrand Diseases

Topics: Air; Culture Techniques; Glycogen; Humans; Lectins; Leukemia, Myeloid; Lymphocyte Activation; Lymphocytes

Topics: Acetates; Aspartic Acid; Carbon Isotopes; Citric Acid Cycle; Glucose; Glutamates; Glycogen; Glycolysis; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lipids; Muramidase; Pentoses

Topics: Adult; Amylases; Bone Marrow; Bone Marrow Cells; Child; Fats; Glycogen; Histocytochemistry; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Periodic Acid; Staining and Labeling

Topics: Acids; Bone Marrow Diseases; Diagnosis, Differential; Glycogen; Humans; Leukemia, Myeloid; Myeloproliferative Disorders; Peroxidases; Polycythemia Vera; Primary Myelofibrosis

Topics: Acute Disease; Adolescent; Adult; Bone Marrow; Bone Marrow Cells; Deoxyuridine; Female; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glycogen; Glycolysis; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; NADP; Nucleosides; Oxygen Consumption; Phosphogluconate Dehydrogenase; Phosphotransferases; Polycythemia; Uridine

Topics: Aged; Blood Glucose; Female; Glucose; Glycogen; Glycolysis; Humans; Hypoglycemia; Infusions, Parenteral; Leukemia, Myeloid; Leukocytes

Topics: Acute Disease; Bone Marrow; Bone Marrow Cells; Glucosyltransferases; Glycogen; Humans; Leukemia; Leukemia, Myeloid; Leukocytes; Nucleotidyltransferases; Oxidoreductases; Oxygen Consumption; Phosphoglucomutase

Topics: Adenosine Triphosphatases; Adult; Alkaline Phosphatase; Autoradiography; Bone Marrow; Bone Marrow Cells; Culture Media; Culture Techniques; Dextrans; Glucocorticoids; Glucosyltransferases; Glycogen; Histocytochemistry; Humans; Leukemia, Myeloid; Leukocytes; Thymidine; Transferases; Tritium

Topics: Adult; Aged; Esterases; Exudates and Transudates; Female; Glycogen; Histocytochemistry; Humans; Inflammation; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Lipids; Male; Middle Aged; NADP; Phagocytosis; Phosphoric Monoester Hydrolases; Skin Window Technique; Succinate Dehydrogenase

Topics: Glucose; Glycogen; Humans; Leukemia, Myeloid; Leukocytes; Ligases

Topics: Glycogen; Histocytochemistry; Humans; Leukemia, Myeloid; Leukocytes; Polycythemia Vera

Topics: Bone Marrow Diseases; Child; Child, Preschool; Clinical Enzyme Tests; Glucosyltransferases; Glycogen; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Myeloproliferative Disorders

Topics: Blood Glucose; Glucose-6-Phosphatase; Glycogen; Glycogen Phosphorylase; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphocytes; Metabolism

Topics: Carbohydrate Metabolism; Fibrinogen; Glycogen; Glycogenolysis; Leukemia; Leukemia, Myeloid; Leukocytes; Povidone; Research; Tissue Culture Techniques

Topics: Autoradiography; Chemical Phenomena; Chemistry; Coloring Agents; DNA; DNA, Neoplasm; Glycogen; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphocytes; Oxidoreductases; Plant Lectins; Staining and Labeling; Thymidine; Tissue Culture Techniques

Topics: Classification; Glycogen; Histocytochemistry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphocytes; Succinate Dehydrogenase

Topics: Alkaline Phosphatase; Blood Chemical Analysis; Bone Marrow Examination; Clinical Enzyme Tests; DNA; Electron Transport Complex IV; Glycogen; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lipids; Oxidoreductases; Peroxidases; RNA

Topics: Clinical Enzyme Tests; Glucosyltransferases; Glycogen; Humans; Leukemia; Leukemia, Myeloid; Leukocytes; Uridine Diphosphate Glucose

Topics: Alkaline Phosphatase; Blood Cells; Endocarditis; Endocarditis, Bacterial; Female; Glycogen; Hepatitis; Hepatitis A; Histocytochemistry; Humans; Infant, Newborn; Infectious Mononucleosis; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Polycythemia Vera; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Primary Myelofibrosis; Sepsis