muramidase and Leukemia--Erythroblastic--Acute

We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enhanced by combined treatment with vesnarinone and retinoic acid. HEL cells are highly resistant to some anticancer drugs, including vincristine, but treatment with vesnarinone greatly increased the sensitivity of HEL cells to vincristine. Enhancement of vincristine sensitivity by vesnarinone was not as significant for other leukemia cells. Expression of P-glycoprotein in HEL cells was effectively inhibited by vesnarinone, suggesting that the restoration of vincristine sensitivity is associated with decrease of P-glycoprotein expression in HEL cells. The plasma level of vesnarinone required to induce differentiation of leukemia cells is 30 micrograms/mL, which could be achieved with oral administration. These results suggest that vesnarinone should be useful in differentiation therapy for some types of myelogenous leukemia.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Calcium; Cardiotonic Agents; Cell Differentiation; Drug Interactions; Drug Resistance; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Muramidase; Pyrazines; Quinolines; Stimulation, Chemical; Tretinoin; Tumor Cells, Cultured; Vincristine

The revised French-American-British (FAB) classification system for acute myeloid leukemia (AML) recommends the determination of serum lysozyme (SL) or urine lysozyme (UL) levels as an aid in distinguishing acute myeloblastic leukemia with maturation (FAB M2) from acute myelomonocytic leukemia (M4). We reviewed retrospectively 208 cases of adult leukemia in which SL and/or UL were obtained. Elevated lysozyme levels were not found in any of the M0, M3, or M7 cases, but were increased (false positive) in three (14%) M1 cases, 18 (19%) M2 cases and one (20%) M6 case. Although a UL value in excess of 3x normal was found in most cases of AML M4 and M5, only five (11%) M4 cases and three (20%) M5 cases had SL elevations of this magnitude. Lysozyme levels need to be interpreted in conjunction with other parameters for FAB classification.

Topics: Aged; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Muramidase

Topics: Animals; Erythroblasts; Female; Granulocytes; Hemoglobins; Immunohistochemistry; Leukemia, Erythroblastic, Acute; Liver; Microscopy, Electron; Muramidase; Rats; Rats, Sprague-Dawley; Spleen

Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7), induced Nitroblue tetrazolium reducing activity, lysozyme activity and morphological maturation of human monoblastic U937, THP-1 and promyelocytic HL-60 cells, but not of erythroblastic K562 cells. However, three analogs of ML-9, which are an inhibitor and an activator of protein kinase C, and a calmodulin antagonist, respectively, did not induce differentiation of the cells.

Topics: Azepines; Cell Differentiation; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Promyelocytic, Acute; Muramidase; Myosin-Light-Chain Kinase; Naphthalenes; Nitroblue Tetrazolium; Oxidation-Reduction; Tumor Cells, Cultured

The bone marrow biopsy specimens of 35 patients with benign and malignant erythroid hyperplasias were examined for the presence of hemoglobin A, hemoglobin F, muramidase (lysozyme), and transferrin, using an indirect immunoperoxidase method (PAP) on Zenker's-fixed paraffin-embedded bone marrow biopsy specimens and particles. Five cases of each of the following entities were studied: erythroleukemia and erythremic myelosis, acute granulocytic leukemia with maturation (FAB M2), polycythemia rubra vera, myeloproliferative syndrome in childhood, megaloblastic anemia (B12 and folate deficiency), erythroid hyperplasia (regenerating bone marrow and hemolytic anemia), and Ph' chromosome positive chronic granulocytic leukemia. Hemoglobin A was present in both the early and late erythroid precursors in all conditions. Hemoglobin F was the predominant hemoglobin in early erythroblasts of pernicious anemia and in both early and late erythroid elements in erythroleukemia and erythremic myelosis. Small quantities of hemoglobin F were present in a few isolated clusters in other conditions. Staining for hemoglobin F may be useful in identifying immature erythroid precursors and in distinguishing some cases of dysplastic erythroid hyperplasia from neoplasia. Additionally, these findings suggest that the maturational switch in hemoglobin synthesis operates with distinct pathways under different conditions.

Topics: Bone Marrow; Bone Marrow Diseases; Fetal Hemoglobin; Hemoglobin A; Histocytochemistry; Humans; Hyperplasia; Immunoenzyme Techniques; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Muramidase; Transferrin

Lysozyme activity was studied in blood smears, serum, and urine of patients suffering from leukaemia or other haematological diseases. Increased enzyme activity was found in myelocytic, myelomonocytic and monocytic leukaemia and equally in secondary granulocytosis and polycythaemia vera. Reduced rates were found in lymphocytie leukaemia, malignant lymphoma with bone marrow involvement, and myelophthisic conditions. A rise in urinary lysozyme occurred when the serum level exceeded 50 microgram/ml. Abundant activities were found in myelomonocytic and monocytic leukaemias. Using the bacteriolytic method in blood smears, no enzyme activity was demonstrated in cells of acute or chronic lymphocytic leukaemia, in monocytic leukaemia however, almost all cells show strong reaction. In acute myelocytic or myelomonocytic leukaemia, the portion of positive cells changes from case to case depending on the degree of cell differentiation and maturation. In chronic myelocytic leukaemia there was no difference as compared to enzyme activity of myelocytes in bone marrow of control cases. Thus the bacteriolytic demonstration of lysozyme in blood smears may additionally contribute to distinction of different types of blastic leukaemias, and serum lysozyme also may allow more reliable insight into granulocytic and monocytic myelopoiesis than morphologic studies of blood or bone marrow smears can do, e.g. in agranulocytosis and pancytopenia.

Topics: Anemia, Aplastic; Hematologic Diseases; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Muramidase; Waldenstrom Macroglobulinemia

Topics: Adolescent; Adult; Aged; Agranulocytosis; Allopurinol; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Blood Transfusion; Cytarabine; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Muramidase; Nausea; Prednisolone; Thrombocytopenia; Vincristine

Topics: Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Monocytes; Muramidase; Myeloproliferative Disorders; Neutrophils; Precancerous Conditions

Topics: Adult; Anemia, Aplastic; Child; Hematologic Diseases; Hodgkin Disease; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemoid Reaction; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Muramidase; Mycosis Fungoides; Myeloproliferative Disorders; Polycythemia Vera