glycogen and Leukemia--Erythroblastic--Acute

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

Although the insulin-dependent hydrolysis of glycosyl-phosphatidylinositol (GPI) may play an important role in insulin action, an absolute requirement for this glycolipid has not been demonstrated. Human K562 cells were mutated to produce a cell line (IA) incapable of the earliest step in PI glycosylation, the formation of PI-GlcNAc. Another cell line (IVD) was deficient in the deacetylation of PI-GlcNAc to form PI-GlcN and subsequent mannosylated species. Each line was transfected with wild-type human insulin receptors. Similar insulin-stimulated receptor autophosphorylation was observed in all three lines, along with a nearly identical increase in the association of phosphorylated insulin receptor substrate 1 with endogenous PI 3-kinase. Both normal and GPI-defective lines also displayed a similar 2- to 3-fold increase in phosphorylation of the Shc protein and its association with growth factor receptor-bound protein 2 in response to insulin. In contrast to these results, striking differences were noted in insulin-stimulated glycogen synthesis. In normal cells, glycogen synthesis was significantly increased by insulin, whereas no insulin stimulation was observed in GPI-deficient IA cells, and only a trace of stimulation was detected in IVD cells. These results indicate that tyrosine phosphorylation produced by insulin is not dependent on GPI synthesis, and this effect is not sufficient to elicit at least some of the metabolic effects of the hormone. In contrast, GPI synthesis is required for the stimulation of glycogen synthesis by insulin in these cells. These findings support the existence of divergent pathways in the action of insulin.

Topics: Cell Line; Flow Cytometry; Glucose; Glycogen; Glycosylphosphatidylinositols; Humans; Insulin; Kinetics; Leukemia, Erythroblastic, Acute; Mutagenesis; Phosphorylation; Phosphotyrosine; Receptor, Insulin; Recombinant Fusion Proteins; Recombinant Proteins; Transfection; Tumor Cells, Cultured; Tyrosine

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: Acetates; Acid Phosphatase; Esterases; Glycogen; Histocytochemistry; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Naphthol AS D Esterase; Peroxidases

Periodic acid-Schiff-positive material representing glycogen was found in bone marrow megaloblasts at all stages of maturation from 11 patients with severe untreated pernicious anemia. This accumulation of glycogen in megaloblasts, which are known to have disordered biosynthesis of DNA, RNA, and histones, suggests that carbohydrate metabolism may also be abnormal in vitamin B12 deficiency, perhaps as a result of an abnormality in the enzyme amylophosphorylase.

Topics: Anemia, Pernicious; Bone Marrow; Bone Marrow Cells; Erythrocytes, Abnormal; Glycogen; Humans; Leukemia, Erythroblastic, Acute; Megaloblasts; Periodic Acid-Schiff Reaction

Topics: Anemia, Aplastic; Anemia, Sideroblastic; Arginine; Chronic Disease; Erythroblasts; Esterases; Glycogen; Histones; Humans; Iron; Leukemia, Erythroblastic, Acute; Methyltransferases; Vitamin B 12

Phosphorylase activity was detected in the cytoplasm of erythroid precursors of 6 of 7 patients with chronic erythremic myelosis (Di Guglielmo syndrome), in proerythroblasts and megaloblasts from 3 patients with pernicious anemia and in 2 patients with severe folate deficiency in neoplastic lymphocytes from 2 patients with acute lymphoblastic leukemia, and in 1 patient with leukemic lymphosarcoma. In all of these patients, most of the erythroid precursors and/or neoplastic lymphocytes contained increased amounts of glycogen when stained with the PAS reagent. Phosphorylase activity was not detected in erythroid precursors obtained from 6 presumed normal individuals or from 3 of 7 patients with a variety of other types of anemia in which the erythroid precursors were PAS-negative. Similarly, phosphorylase activity was absent in lymphocytes obtained from presumed normal individuals. Although the mechanisms responsible for the pathogenesis of PAS positivity are unclear, it is possible that the increased phosphorylase activity found in cells that are PAS-positive may reflect a disorder in the biosynthetic pathway of glycogen.

Topics: Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Anemia, Pernicious; Bone Marrow; Bone Marrow Cells; Erythroblasts; Folic Acid Deficiency; Glycogen; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Phosphorylases; Spherocytosis, Hereditary; Staining and Labeling

Cytochemical properties of atypical erythroblasts and 'histioid' cells from the bone marrows of two patients with acute erythremic myelosis (Di Guglielmo's disease) were studied. In addition to strong PAS and strong nonspecific esterase positivity, intense specific esterase positivity was also detected in the majority of the erythroid precursors. Since specific esterase activity is considered to be a feature of granulocytic cells, its presence in erythroid precursors raises the possibility that the atypical erythroblasts of acute erythremic myelosis may share close metabolic relationships with granulocytic cells.

Topics: Acute Disease; Aged; Bone Marrow; Erythroblasts; Erythrocytes; Esterases; Female; Glycogen; Granulocytes; Humans; Leukemia, Erythroblastic, Acute; Phosphorylases

Topics: Adolescent; Aged; Bone Marrow; Bone Marrow Cells; Clone Cells; Cyclophosphamide; Cytarabine; Erythrocytes, Abnormal; Glycogen; Histocytochemistry; Humans; Leukemia, Erythroblastic, Acute; Male; Microscopy, Electron; Prednisone; Vinblastine; Vincristine

Topics: Adult; Aged; Carbohydrate Metabolism; Erythrocytes; Female; Glycogen; Glycolysis; Histocytochemistry; Humans; Leukemia, Erythroblastic, Acute; Male; Middle Aged; Mucoproteins

Topics: Anemia; Anemia, Hypochromic; Blood Chemical Analysis; Erythrocytes; Glycogen; Hematologic Diseases; Humans; Leukemia, Erythroblastic, Acute; Thalassemia