Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A congenital erythrocyte pyruvate kinase (PK) deficiency was found in a 72-year old female patient with chronic myelomonocytic leukemia (CMML). Erythrocyte PK deficiency was associated with an increase in the activity of hexokinase, 6-phosphogluconate dehydrogenase and glutathione peroxidase in erythrocytes as well as a decrease in acetylcholinesterase, glutathione reductase and glucosephosphate isomerase activities. The enzymatic abnormalities were accompanied by alterations in hemoglobin and in i antigen content of erythrocyte membrane. In addition, bone marrow ultrastructural studies showed dyshemopoietic changes in all blood cell lines and especially in erythroblasts. The present findings confirm the close relationship between CMML and acquired dyserythropoietic syndromes and constitute a new observation of the infrequent association of hereditary erythrocyte enzymopathies and leukemia. A survey of the literature is presented.
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PMID:Chronic myelomonocytic leukemia associated with hereditary pyruvate kinase deficiency and multiple acquired erythrocyte abnormalities. 10 94

Seventy-one male and 52 female F 344 rats with leukemia used as controls in the 30-month inhalation studies were characterized by hematological and clinico-biochemical findings. Hematological findings revealed that the leukocyte count, mean corpuscular volume, and mean corpuscular hemoglobin increased in both sexes of leukemic rats showing profound anemia, while the platelet count, erythrocyte count, hematocrit, and hemoglobin concentration decreased. In these rats, the serum levels of low density lipoprotein, free cholesterol, total bilirubin, blood urea nitrogen, and triglyceride and the activities of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, creatine phosphokinase, alkaline phosphatase, and lactate dehydrogenase increased markedly and the level of high density lipoprotein, the oxygen partial pressure, and the cholinesterase activity decreased. Clinical signs such as decrease in redness of the eyes, decrease in body weight, abdominal distension, staining of the public region, and debility were seen in most leukemic animals. These clinical signs and hematological and clinico-biochemical findings may be helpful in diagnosis of leukemia in long-term experiments.
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PMID:Hematological and clinico-biochemical characteristics of leukemia in Fischer 344 rats. 150 22

Mouse C1 line cells are megakaryoblastic cells established by coinfection of Abelson murine leukemia virus and recombinant simian virus 40. We examined the effects of various compounds on growth and differentiation of these cells. Megakaryocytic differentiation of C1 cells was not induced by cytokines that stimulate megakaryocytic maturation of normal progenitor cells, such as interleukin 3 and 6 and granulocyte-macrophage colony-stimulating factor. However, the cells were induced to differentiate into megakaryocytes by treatment with some protein kinase inhibitors. The inhibition of v-abl tyrosine kinase activity preceded induction of differentiation of the cells treated with tyrosine kinase inhibitors such as genistein, herbimycin A, and erbstatin. Treatment of C1 cells with a v-abl antisense oligomer inhibited their proliferation and induced acetylcholinesterase activity, a typical marker of megakaryocytic differentiation. These results suggest that inhibition of v-abl function is associated with induction of megakaryocytic differentiation of C1 cells. Among the compounds tested, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of cyclic nucleotide-dependent and Ca(2+)-phospholipid-dependent (protein kinase C) protein kinases, was the most potent inducer of differentiation of C1 cells. However, the differentiation-inducing effect of H-7 was unlikely to be mediated through inhibition of protein kinase C or cyclic nucleotide-dependent kinases, because other types of inhibitors of these kinases were not effective, and a protein kinase activator (phorbol ester) induced differentiation of C1 cells. Moreover, neither v-abl mRNA expression nor v-abl kinase activity in C1 cells was affected by treatment with H-7. These findings indicate that induction of megakaryocytic differentiation by H-7 is not related to inhibition of v-abl kinase, but rather to some novel function of H-7.
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PMID:Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with Abelson murine leukemia virus and recombinant SV40 retrovirus. 165 10

Dichlorvos (dichlorovinyl dimethyl phosphoric acid ester) is a cholinesterase inhibitor used widely as a contact and stomach insecticide for control of internal and external parasites. Carcinogenesis studies were conducted by administering dichlorvos in corn oil by gavage 5 times a week for 103 weeks to groups of 50 male and 50 female Fischer rats at 0, 4, or 8 mg/kg body weight, to groups of 50 male B6C3F1 mice at 0, 10, or 20 mg/kg, and to groups of 50 female B6C3F1 mice at 0, 20, or 40 mg/kg. During the course of the studies, body weights and survival rates of the male and female rats and mice were not different from those of their respective controls; females of both species appeared to gain more weight than controls. Neoplasms induced by dichlorvos included adenomas of the exocrine pancreas (male rats), mononuclear cell leukemia (male rats), and squamous cell papilloma of the forestomach (male and female mice; two other female mice had squamous cell carcinomas). Lesions observed in female rats that may have been due to dichlorvos administration included adenomas of the exocrine pancreas and fibroadenomas of the mammary gland. The results demonstrated that dichlorvos is carcinogenic for Fischer rats and B6C3F1 mice.
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PMID:Carcinogenesis studies of dichlorvos in Fischer rats and B6C3F1 mice. 190 Aug 19

A murine megakaryoblastic cell line growing in protein-free culture (L8057Y5) was established from an experimentally induced murine leukemia (MK8057). Most of the Y5 cells were small and blast-like, with 2-4N in DNA content. Also, large cells possessing a lobulated nucleus characteristic of megakaryocytes, which showed polyploidization to more than 4N up to 16N, were occasionally seen. Nearly 5% of the total number of Y5 cells were positive for acetylcholinesterase reaction. The survival time of C3H/He mice after injection with Y5 cells was longer than that of mice injected with the original MK8057 cells. The colony-forming ability of Y5 cells in the spleen of the lethally irradiated mouse was much lower, whereas the number of in vitro colonies derived from Y5 was greater than that of MK8057. The plating efficiency of colony formation in serum-free methylcellulose culture was higher at a low O2 tension. Conditioned medium of Y5 cells enhanced colony formation as well as 3H-TdR uptake by Y5 cells, which implies that Y5 cells may produce autocrine growth factor(s). mRNAs for IL-6, LIF, and INF-gamma were expressed in Y5 cells; these cytokines may have roles in the growth mechanisms of the cell line.
Leukemia 1991 May
PMID:Establishment and characterization of a murine megakaryoblastic cell line growing in protein-free culture (L8057Y5). 190 80

A series of 5- and 6-substituted cyclophosphamide analogues has been prepared, and their 31P NMR kinetics of phosphoramide mustard (PDA) release and in vitro and in vivo cytotoxicity have been evaluated. cis-4-Hydroxy-5-methoxycyclophosphamide equilibrated very slowly and to a minor extent with the ring-opened aldophosphamide analogues in aqueous buffer; release of PDA was observed to a minor extent and only at high (1 M) buffer concentrations. This analogue was essentially inactive in vitro against L1210 and P388 leukemia cells. 6-Phenylcyclophosphamide and its 4-hydroperoxy derivative were potent inhibitors of blood acetylcholinesterase and were lethal at therapeutic doses in mice. In contrast, 4-hydroperoxy-6-(4-pyridyl)cyclophosphamide did not inhibit acetylcholinesterase and showed significant antitumor activity in vitro and in vivo against both wild-type and cyclophosphamide-resistant L1210 leukemia. The 4-hydroperoxy-6-arylcyclophosphamides were generally active in vitro against both wild-type and cyclophosphamide-resistant L1210 and P388 cells, and several analogues showed significant activity in vivo. Surprisingly, there was no correlation between antitumor activity in vitro and the rate of PDA release in aqueous buffer. Several compounds that showed essentially no release of PDA in aqueous buffer over several hours were highly cytotoxic to leukemia cells following a 1-h exposure in vitro. These results show that activated cyclophosphamide analogues substituted at the 6-position are not cross-resistant in these leukemia cell lines, and that a specific intracellular activation mechanism may be catalyzing PDA release in these analogues.
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PMID:Synthesis and antitumor properties of activated cyclophosphamide analogues. 192 Mar 55

Five cases of murine leukemia with megakaryocytic differentiation were observed among the 417 cases of radiation-induced leukemias which developed in 30% of C3H/HeMs mice exposed at 8 to 10 weeks to 0.5 to 5 gy total body irradiation. Cells from individual leukemic colonies in the spleen of the irradiated mice, and cells from colonies in methylcellulose (MC) culture in vitro, derived from one of these leukemias, MK-8057, were injected into mice; both types of cells caused the deaths of the recipient mice by inducing the same type of leukemia. MK-8057 can be maintained in Dexter-type liquid culture with a feeder layer of irradiated bone marrow cells. There was a linear reciprocal relationship between the increasing number of MK-8057 cells injected versus the survival of the recipient mice. A reciprocal relationship also was seen between an increasing number of leukemic stem cells, corresponding to the number of MK-8057 cells, and the survival of mice injected with MK-8057. Giant nuclear megakaryocytes developed during the course of colony growth in the spleen as they did in the MC culture. Such megakaryocytes were acetylcholinesterase positive, whereas leukemic cells in the peripheral blood showed no sign of platelet production nor of a positive reaction to acetylcholinesterase. Cells maintained in culture were entirely positive in platelet glycoprotein IIb/IIIa when anti-human antibody was used. The larger cells in a splenic cell suspension derived from a moribund mouse were separated and enriched by velocity sedimentation using centrifugal elutriation (CE), and then subjected to flow cytometry using propidium iodide staining. Cells with up to 32N-DNA content were detected. After separating MK-8057 by counter-flow CE, the larger cell fraction (mode at 540 microns3) produced more leukemic colonies when injected into irradiated mice than did the small cell fraction (mode at 240 microns3). A higher percent of the larger cell fraction (61.9%) was killed by the addition of tritiated thymidine cytocide than in the smaller cell fraction (14.9%). Thus, the smaller cell fraction is considered to have more leukemic spleen colony-forming units (L-CFU-s) in the resting state.
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PMID:Murine acute leukemia cell line with megakaryocytic differentiation (MK-8057) induced by whole-body irradiation in C3H/He mice: cytological properties and kinetics of its leukemic stem cells. 201 Jun 53

Systematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X:C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X:C 55%-68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X:C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.
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PMID:Coincidence of acquired factor-X deficiency and disseminated intravascular coagulation in patients with acute nonlymphoblastic leukemia. 204 64

In 34 patients (16 women and 18 men) with acute leukaemias (8 with acute lymphoblastic leukaemia and 26 with acute myeloblastic leukaemia), as yet untreated, the serum levels were determined of conjugated cholic acid, bilirubin, aspartate aminotransferase (AspAT), alanine aminotransferase (AlAT), alkaline phosphatase (AP), lactate dehydrogenase (LDH) and cholinesterase (Chol). Serum conjugated cholic acid level was determined by radioimmunoassay. The mean values of AP and Chol activity were within the range of normal values in this laboratory, the values of AspAT and AlAT were slightly above this range, and LDH value exceeded twice this normal range. The mean bilirubin concentration was within normal range. The greatest changes were noted in conjugated cholic acid values, the mean value exceeded five times the upper normal range (1.0 mumol/l). In 30 patients (88%) the conjugated cholic acid level in the serum was above 1.0 mumol/l, in the remaining 4 cases it was above the mean value for the control group. No correlation was found between conjugated cholic acid and any of the determined parameters. These results point out that the serum level of conjugated cholic acid may be a valuable parameter for assessment of hepatocellular function in acute leukaemias.
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PMID:[Serum cholic acid levels in patients with acute leukemia]. 225 Dec 7

With the aim of increasing the selectivity of the 2,2-dimethylphosphoraziridine type antitumor agents toward the intracellular site of DNA synthesis, a series of new compounds was synthesized in which the reactive bis(2,2-dimethyl-1-aziridinyl)phosphinyl (2,2-DMAP) group was linked through a carbamate or amide linkage to thymidine or cytosine nucleoside moieties. The 3'- and 5'-(2,2-DMAP)carbamates of thymidine (1 and 2) were found to be highly unstable, therefore the corresponding O-acetyl derivatives 5 and 6 were prepared by reacting 5'- and 3'-acetylthymidine, respectively, with dichloroisocyanatophosphine oxide followed by the addition of 2,2-dimethylaziridine and triethylamine. The 3'- and 5'-(2,2-DMAP)amides of thymidine 14 and 15 were prepared by reacting the appropriate thymidinylamines with bis(2,2-dimethyl-1-aziridinyl)phosphinyl chloride (17). The N4-(2,2-DMAP)amides of cytidine, 2'-deoxycytidine, and cytosine arabinoside (18, 19, and 20, respectively) were prepared by reacting the hydrochlorides of the O-peracetylated cytosine nucleosides with triethylamine and POCl3 and, subsequently, with 2,2-dimethylaziridine and triethylamine, to give the corresponding N4-(2,2-DMAP)cytosine nucleoside peracetates 21, 22, and 23, respectively, which were then deacetylated by aminolysis. However, the peacetate intermediates were found to be more stable and, probably for the same reason, also more active against P388 leukemia in mice than the deacetylated products. Particularly, 22 and 23 showed sufficient activity in this in vivo assay system to warrant further evaluation. The relationships between the antitumor activities, the chemical alkylating activities, and the cholinesterase inhibitory activities of these agents are discussed.
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PMID:Synthesis of new nucleoside phosphoraziridines as potential site-directed antineoplastic agents. 239 98


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