Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosine arabinoside (araC) has proven efficacy in acute myeloid leukemia (AML), but its place in the treatment of acute lymphoblastic leukemia (ALL) and T lymphoblastic lymphoma is uncertain. The therapeutic potential of araC has been assessed in patients with AML, ALL, and T lymphoblastic lymphoma by measuring the conversion of araC to its active metabolite, the 5'-triphosphate of araC (araCTP), in purified blasts from patients as well as in normal polymorphs and lymphocytes. In all leukemias, araCTP was the major intracellular metabolite of araC. The highest araCTP formation was in blasts from T lymphoblastic lymphoma, which formed threefold more nucleotide than myeloblasts, and in turn myeloblasts formed twofold more araCTP than lymphoblasts from ALL. The mean araCTP formation in myeloblasts was sixfold greater than polymorphs, but in contrast, lymphoblasts and lymphocytes formed low and similar amounts of this nucleotide. Reasons for the sixfold range in araCTP accumulation in the various leukemic blasts were studied. The mean size of myeloblasts was 35-70% larger than lymphoblasts when compared on the basis of protein or intracellular water content, but T lymphoblastic lymphoma blasts and lymphoblasts were the same size. Activities of deoxycytidine kinase, deoxycytidylate deaminase, and pyrimidine nucleoside monophosphate kinase were not different between any of the leukemic cell types. The number of nucleoside transport sites on blasts was estimated by measuring the equilibrium binding of [3H]nitrobenzylthioinosine (NBMPR), which binds with high affinity to the transporter. Scatchard analysis yielded mean values of 27,500 sites/cell for T lymphoblastic lymphoma blasts, 10,000 sites/cell for myeloblasts, and 2,300 sites/cell for lymphoblasts. Our previous work has shown that araC influx correlates with the maximum number of 3H-NBMPR binding sites in leukemic and normal white cells. A strong correlation was observed between the number of nucleoside transport sites per leukemic blast cell and the accumulation of intracellular araCTP from extracellular araC at 1 microM. Membrane transport of araC at the low concentrations (approximately 1 microM), which are achieved therapeutically, is a major rate-limiting step in its conversion to araCTP by leukemic blast cells. Myeloblasts form more araCTP than lymphoblasts because of both higher nucleoside transport capacity and larger cell size. The highest nucleoside transport capacity and largest conversion of araC to araCTP is in T lymphoblastic lymphoma, which suggests that araC may be effective in the treatment of this disease.
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PMID:Cytosine arabinoside transport and metabolism in acute leukemias and T cell lymphoblastic lymphoma. 387 94

Hyponatraemia was observed in 11 out of 14 consecutive patients with acute myeloid leukaemia and its variants. Metabolic studies on these patients revealed an early increase in the urinary sodium excretion, negative free water clearance, and urine osmolality inappropriately higher than that of the serum. It is postulated that this syndrome is caused by a substance released from the primitive cells of the abnormal myeloid series.
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PMID:Hyponatraemia syndrome in acute myeloid leukaemia. 452 14

In animal models of cancer, an elevation of T1 and T2 in uninvolved tissues and in the blood of tumor bearing animals has been termed "the systemic effect." This study reports T1 values in sera of human patients from Genoa, Italy, with several types of cancer and non-cancerous diseases. T1 values were significantly elevated over normal controls (1628 +/- 113 ms) in colorectal cancers (1725 +/- 149 ms) and stomach cancers (1817 +/- 219 ms). However a systemic effect was not demonstrated in acute myeloid leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, or plasma cell myeloma, or in pancreatic and lung cancers. Noncancerous states of cirrhosis, chronic hepatitis, and monoclonal gammapathies did not show a T1 elevation. In general, T1 values of sera correlated with protein content of the sera; however, a disproportionate contribution of gamma-globulin protein on water proton relaxation times was observed in several cases.
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PMID:The systemic effect of cancers on human sera proton NMR relaxation times. 608 32

A monoclonal antibody (MAb) HL-C5, which bound selectively to cells of the myeloid lineage tested, was derived from a fusion between P3/NS2/1-AG8 myeloma cells and splenocytes from a mouse immunized with cells of the promyelocytic leukemia line HL-60. Among a panel of 29 human cell lines derived from either hematopoietic or solid tumors, MAb HL-C5 was found to react exclusively with cells from the five differentiated acute myeloid leukemia lines, HL-60, ML1, ML2, ML3, KG-1B and not with the less differentiated myeloid lines. Fluorescence-activated cell sorter analysis of normal bone marrow samples confirmed that the reactivity of MAb HL-C5 was limited to myeloid cells, from the promyelocytic stage of differentiation to the mature granulocytes. Indirect immunoperoxidase staining of cytocentrifuge preparations of normal bone marrow and peripheral blood leukocytes confirmed these results and showed that MAb HL-C5 stained neutrophils but not eosinophils or basophils. The antigen recognized by HL-C5 was recovered in the upper phase of chloroform-methanol-water lipid extracts prepared from HL-60 cells. By competitive binding experiments, it was found that MAb HL-C5 recognizes the same antigenic determinant as MAb WGHS 29-1, which has been reported to react with glycolipids containing the sugar sequence lacto-N-fucopentaose 111. Autoradiographs of thin layer chromatograms of HL-60 glycolipid extracts which were revealed by incubation with MAb HL-C5 or WGHS 29-1 followed by the addition of 125I-labelled rabbit anti-mouse immunoglobulin antibody confirmed that the two MAbs reacted with the same or structurally very similar glycolipids.
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PMID:Identification by a monoclonal antibody of a glycolipid highly expressed by cells from the human myeloid lineage. 657 67

A rapid and selective high-performance liquid chromatographic method for the measurement of 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA), a new anticancer drug, has been developed. The method employed an analogue of AMSA, 4'-(3-methyl-9-acridinylamino)methanesulphonanilide as internal standard. Plasma samples were acidified, washed with hexane, readjusted to pH 9.0 and extracted with diethyl ether. The evaporated extract was chromatographed on a Radial-Pak C18 column using acetonitrile--water containing 0.01 mol/l triethylamine phosphate as mobile phase. Detection was by UV absorbance at 254 nm. Chromatography time for each sample was 5.5 min. Using 0.5 ml of plasma, AMSA concentrations as low as 50 nmol/l could be measured with acceptable accuracy and precision. Patients samples remained stable when stored at -20 degrees C for up to one month. Plasma AMSA concentrations were followed for 24 h after 200 mg/m2 infusions in two patients with acute myeloid leukemia. This method appears eminently suitable for investigation of the pharmacokinetics of AMSA in patients and laboratory animals.
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PMID:High-performance liquid-chromatographic method for the determination of 4'-(9-acridinylamino)methanesulfon-m-anisidide in plasma. 668 11

Leukocytes were obtained from 14 healthy subjects, one patient with the infantile form, two patients with the adult variant of acid maltase deficiency, two patients with chronic myelocytic leukemia, two patients with acute myeloid leukemia, and two patients with chronic lymphotic leukemia. In addition, lymphocytes were prepared from three normal subjects, and five established lymphoid lines were used. Cells were extracted either with Triton 0, 2%, or with water followed by 0.2% Triton. alpha-Glucosidase activity was measured in water homogenates, water extracts after centrifugation, and Triton extracts, with or without antisera directed against acid maltase (EC 3.2.1.3) and renal maltase (EC 3.2.1.20). The percentage of acid and renal maltases was then calculated in each soluble fraction. Normal whole leukocytes (mostly granulocytes) contain both acid and "renal" maltases, whereas normal lymphocytes contain very little or no "renal maltase." This isozyme is present in chronic myelocytic leukemia, but is absent in acute myeloid and chronic lymphocytic leukemia as well as in established lymphoid lines. Acid maltase is almost completely extracted with water, whereas renal maltase is extracted only with Triton. From the results, it appears that for the diagnosis of alpha glucosidase deficiency, cells should be extracted in water and centrifuged before determination. Lymphocytes, which are devoid of renal maltase, are a better diagnostic material than are granulocytes.
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PMID:White blood cells and the diagnosis of alpha-glucosidase deficiency. 676 91

Pulsed nuclear magnetic resonance studies have been carried out on bone marrow of normal human subjects and patients with leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). It was observed that the proton spin-lattice relaxation time (T1) value was discriminatory in the normal and leukemic cases with a statistical significance of (p less than 0.01). Ouabain treatment of cells did not show any perceptible change of T1 value when compared with the nontreated cells, indicating that the concomitant cation effluxes do not affect spin-lattice relaxation time. The water contents of normal, leukemic, and ouabain treated cells were in the range 60%-80%. Higher Fe levels were encountered in the normal than the leukemic samples, while levels of Zn, Cu, Mn, Co, and Ni were elevated in the leukemic samples compared with the normals. Despite the T1 differences observed, the multiparameter studies do not uniquely pinpoint factors responsible for the elevation of T1 in the malignant state.
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PMID:Distinction between normal and leukemic bone marrow by water protons nuclear magnetic resonance relaxation times. 696 35

Selected dietary risk factors and other environmental factors were studied in 119 adult patients (60 males and 59 females of the Cracow region) with acute leukaemia (91 acute myeloid leukaemia and 28 acute lymphoblastic leukaemia), by a case-control study method and logistic regression modelling of the risk of leukaemia. It was shown that the diet of patients with acute leukaemias before the onset of the disease differed qualitatively and quantitatively from that of healthy subjects of control groups. The risk of acute leukaemia was elevated in the subjects characterized by rare consumption of raw vegetables, frequent drinking of milk, frequent consumption of poultry, and drinking of soft water. Other environmental conditions connected with the dietary risk were: frequent viral infections, vaccination with the vaccinia virus, frequent use of aminophenazone, presence of fungi in the house, drinking of milk supplied from own's own cows, and frequent deaths of reared poultry.
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PMID:Dietary and other environmental risk factors in acute leukaemias: a case-control study of 119 patients. 846 64

Confocal microspectrofluorometry allows the analysis of fluorescent molecules such as anthracylines in isolated living cells. An optical microscope fitted with a phase-contrast 100 X water-immersion objective enables simultaneous observation of the sample, focusing of the laser beam on the selected cell fraction (nucleus) and collection of the fluorescence emitted from the sample. The resulting intranuclear spectra are interpreted according to a quantitative model of the fluorescence spectra of both free and DNA-bound anthracycline. The intranuclear drug concentration can thus be determined. This technique has been applied to blast cells collected in patients with acute leukemia. Leukemic cells are aspirated from bone marrow, separated by Ficoll sedimentation and resuspended in RPMI-1640 containing 10% fetal calf serum and 200 nM tetrahydropyranyl-doxorubicin (THP-DOX). After one hour, 20 cells are analyzed and the mean nuclear drug content is determined (C1). Cells are then resuspended in the same medium but without anthracycline for 3 hours and the mean intranuclear drug concentration is then also determined (C3). From C1 and C3 the retention rate (RR) is calculated. Firstly, the accuracy of the method was checked. In 4 AML patients, two different samples aspirated on the same day were divided into two portions. Thus, two measurements were made on each one (4 values per patient). Coefficients of variation were satisfactory (4, 6, 12, and 12%). Secondly, blast cells collected in patients with AML and ALL at diagnosis or in relapse were studied. P-glycoprotein (P-gp) and CD34 expression was also studied using respectively immunohistochemistry land flow cytometry. Results obtained from the first 21 patients showed that there was no correlation between RR and either P-gp or CD34 expression. This could result from the efflux of THP-DOX by other mechanisms and/or low sensitivity of the staining technique.
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PMID:[Evaluation of multidrug resistance phenotype on medullary specimens from patients with acute leukemia by determination of nuclear efflux of tetrahydropyranyl-doxorubicin. Approach by confocal laser microspectrofluorometry]. 873 89

This report describes a case of diabetes insipidus associated with acute myelogenous leukemia. An 11-year-old boy presented with fatigue, polydipsia and polyuria. His evaluation revealed a diagnosis of acute myelogenous leukemia FAB-M2, and a water deprivation test confirmed the diagnosis of central diabetes insipidus. His brain magnetic resonance imaging (MRI) showed a thickened, enhancing pituitary stalk with absence of the normal hyperintense signal in the posterior pituitary. He was treated with systemic chemotherapy, intensive intrathecal therapy, and 1,000 cGy to the pituitary. The patient achieved a remission but continued to need desmopressin therapy to control his diabetes insipidus. Diabetes insipidus is a rare complication of acute myelogenous leukemia that can be caused by leukemic infiltration of the pituitary. The diabetes insipidus is irreversible despite intensive systemic and central nervous system chemotherapy and radiation.
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PMID:Diabetes insipidus as a presenting symptom of acute myelogenous leukemia. 1103 61


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