Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deoxycytidine kinase, which phosphorylates deoxycytidine (CdR) and its analog, cytosine arabinoside (ara-C), has been purified 71-fold from human leukemic cells. Biochemical properties of the partially purified enzyme included a molecular weight of 68,000, Kms of 7.8 muM for CdR and 25.6 muM for ara-C, and optimal activity with ATP and GTP as phosphate donors. Ara-C phosphorylation was strongly inhibited by CdR (Ki = 0.17 muM) and dCTP (Ki = 7.3 muM) and was weakly inhibited by ara-CTP (Ki = 0.13 mM). Purification by calcium phosphate gel elution and DEAE chromatography effectively separated this enzyme from cytidine deaminase, which deaminates both CdR and ara-C, and from uridine-cytidine kinase, the enzyme which phosphorylates 5-azacytidine. CdR kinase activity was found to decrease and cytidine deaminase to increase with maturation of normal and leukemic granulocytes. Myeloblasts purified by Ficoll sedimentation revealed an average kinase activity of 15.4 U/mg protein in acute myelocytic leukemia and 12.3 U/mg protein in blastic crisis of chronic myelocytic leukemia (CML). The average ratio of CdR kinase to deaminase activity in crude cell extracts varied from 0.197 in AML and 0.089 in blastic crisis to 0.0004 in normal granulocytes, reflecting the changes which take place with cellular maturation. The absolute levels of kinase and deaminase and the ratio of these two enzymes varied considerably among patients with AML, indicating that quantitative differences may be found in the metabolism of CdR and its analogs in leukemic cells.
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PMID:Deoxycytidine kinase: properties of the enzyme from human leukemic granulocytes. 5 55

Low pH eluates were prepared from trophoblasts derived from 8 term human placentas. A qualitative analysis for immunoglobulins revealed the presence of IgG, IgA, and IgM in these eluates. IgC-rich fractions were obtained by DEAE-cellulose chromatography of ammonium sulfate-concentrated eluates. These fractions were able to neutralize, in vitro, the catalytic activity of reverse transcriptases (RT) from several retroviruses. RT from baboon endogenous virus (BEV) seemed to be more susceptible to the neutralizing activity of some eluates. This was in contrast to RT from feline leukemia virus (FeLV) which were neutralized by eluates of leukocytes from chronic myelogenous leukemia. In contrast to previous and present results with purified IgG from leukemic leukocytes, the purified IgG from placenta eluates was incapable of RT neutralization. However, such purified IgG fractions inhibited mixed lymphocyte reactions.
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PMID:Placenta-bound immunoglobulins. 9 19

The subunit composition of phosphofructokinase from normal and malignant blood cells has been investigated by means of immunologic, electrophoretic, and chromatographic methods. Immunoprecipitation tests were performed with three specific antisera recognizing each of the basic subunits of human phosphofructokinase: muscle, M-type; liver, L-type; and fibroblast, F-type. Mature polymorphonuclear cells contain mainly L-subunits, while lymphocytes and platelets contain hybrids formed of L and F subunits; these hybrids can be electrophoretically separated. Red cell phosphofructokinase is composed of L and M subunits, as judged by its reactivity with anti-L and anti-M-type antisera. The various M-L hybrids composing red cell phosphofructokinase could be only separated by chromatography on DEAE-Cellulose. Lymphocytes from patients with chronic lymphocytic leukemia and lymphoblasts from patients with acute lymphoblastic leukemia contain phosphofructokinase forms similar to those from normal lymphocytes, while the immature granulocytic cells (leukemic myeloblasts and myeloid cells of chronic myeloid leukemia) are characterized by a reinforcement of enzyme inhibition by anti-F-type antiserum. Lymphoid lines in culture (Epstein-Barr virus (EBV)-induced or malignant lymphoma-derived lines) are characterized by the indistinctive expression of all three basic subunits, similar to that found in some fetal tissues. This article represents the first description of the isozymic nature of phosphofructokinase in platelets and white blood cells and of its changes with malignancy and cell culture. This enzyme might represent a useful marker in the characterization of the leukemic cells.
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PMID:Phosphofructokinase in human blood cells. 15 68

Arginase has been isolated from granulocytes of a patient with chronic myelocytic leukemia and from lymphocytes of a patient with chronic lymphocytic leukemia and both enzymes have been purified to apparent homogeneity. The purification procedure employed acetone extraction, ammonium sulfate precipitation, DEAE-cellulose and CM-Sephadex chromatography and gel filtration on Bio-Gel A 1.5m. Both enzymes appear to be metalloenzymes, and to have molecular weights of about 120 000. Studies with the dissociated enzymes suggest that the subunit molecular weight is about 37 000, in agreement with a tetrameric aggregate structure of the native enzymes. Human leukemic granulocyte and lymphocyte arginases are strongly basic proteins with pI values between 9.25 and 9.35. Their free -SH groups enabled them to be linked to organomercurial-agarose. The kinetic properties estimated for both enzymes showed an optimum pH of 8.5, and an optimal MnCl2 concentration of 0.01 M. The Km for L-arginine is 2.7-3.1 mM and L-ornithine exhibits a mixed type of inhibition, with a Ki of 15.5-15.7 mM.
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PMID:Purification of arginases from human-leukemic lymphocytes and granulocytes: study of their physicochemical and kinetic properties. 24 Jul 2

Folate-binding protein(s) from chronic myelogenous leukemia cells have been purified using acid dialysis, ammonium sulfate fractionation and affinity chromatography. The purified preparation which migrates as a single band on disc electrophoresis could be separated by DEAE agarose chromatography into two folate-binding proteins (binders I and II) which bind molar equivalents of folic acid. One binder (I) eluted from DEAE at 1 mM sodium phosphate, pH 6.0, and the other (II) at 100 mM sodium phosphate, pH 7.4. Analysis of the purified mixture, which contained more than 90% binder II, by sedimentation equilibrium centrifugation indicated a homogeneous protein with a calculated molecular weight of 44000. Antiserum raised against the purified mixture gave a single precipitin line by immunodiffusion against a preparation of partially purified cell lysate. Hydrolysis of the more acidic binder (II) with neuraminidase converted it to a weakly acidic protein similar to binder I, suggesting that these binders are glycoproteins which differ in sialic acid content. With isoelectric focusing, the binding of folic acid could be demonstrated at pH 6.7, 7.3, 7.8 and 8.2 for binder I, and at pH 5.1, 5.8, and 6.5 for binder II. Binders I and II had equally high affinity for folic acid and dihydrofolate, lower affinity for N5-methyl-tetrahydrofolate, and no apparent affinity for N5-formyltetrahydrofolate or methotrexate.
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PMID:Properties of purified folate-binding proteins from chronic myelogenous leukemia cells. 28 Mar 77

Human granulocyte catalase (hydrogen peroxide:hydrogen peroxide oxidoreductase, EC 1.11.1.6) was purified from chronic myeloid leukemia cells. The purification procedure included heat precipitation, ammonium sulphate fractionation, DEAE-Sephadex chromatography, gel chromatography on Sephadex G-200 and isoelectric focusing with an approximate yield of 30% and a 1000-fold purification. The molecular weight of the subunit obtained by sodium dodecyl sulphate electrophoresis was 65 800. So20,w was 11.6 +/- 0.24. The pH-optimum was 6.6-6.7 and the spectrum showed a major peak at 405 nm and shoulders at 500, 540 and 625 nm typical for catalase. The electrophoretic mobility was towards the anode at pH 8.6 and identical to normal granulocyte and erythrocyte catalase. These three species of catalase gave the reaction of identity on immunodiffusion and crossed immunoelectrophoresis. The content of catalase and its activity of isolated granulocytes were approximately identical in normal and chronic myeloid leukemia granulocytes while the specific activity of leukemic catalase was higher than normal. No difference in catalase content was found between mature and immature leukemic granulocytes.
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PMID:Purification of human granulocyte catalase in chronic myeloid leukemia. 40 30

Chronic granulocytic leukaemia (CGL) cells which contained a high concentration of unsaturated folate binding protein were incubated in suspension culture for a period of 5 h. Cell samples were periodically assayed for binder and these demonstrated active synthesis which was inhibited by puromycin, cyclo heximide, N-ethylmaleimide, and by incubation at 4 degrees C, but not by actinomycin D. Folate binding activity could also be demonstrated in the culture medium and this increased with the duration of incubation. This release of binder was inhibited by culturing the cells at 4 degrees C and by the addition of N-ethylmaleimide, but not by actinomycin D, puromycin, or cycloheximide. When the pre- and post-culture cell lysates were saturated with tritiated folic acid ([3H]PteGlu) and subjected to chromatography on DEAE-agrarose, approximately half of the bound folate eluted with 0.001 M phosphate buffer at pH 6.0 and the other half eluted with 0.2 M buffer at pH 7.2. The culture medium and plasma from this patient with CGL was well as serum from two normal subjects saturated with [3H]PteGlu and similarly chromatographed contained primarily the acidic binder and much less of the binder eluting with the low molarity buffer. Since a folate binding protein immunochemically similar to the binder in CGL cells has been identified in the serum of non-leukaemic subjects, these experiments suggest that the source of circulating folate binding protein may be the immature granulocyte.
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PMID:Studies with the folate binding protein in chronic granulocytic leukaemia cells. I. Synthesis and release of binder by cells in short-term culture. 106 9

Previous studies have demonstrated that some chronic myelogenous leukemia cells contain a macromolecular binding factor for folic acid. This binder, which previously was believed to be a single factor, has now been resolved into two distinct binding proteins. Separation of each binder was obtained by DEAE chromatography of the partially purified lysate of chronic myelogenous leukemia cells. One binder has a molecular weight of 30;000-35,000, and the second binder has a molecular weight of 40,000-45,000. Both proteins bind the mono-, di-, and triglutamates of folic acid, N10-methyl-folate, dihydro-folate, and N5-methyltetrahydrofolate. Neither binder has determinants for N5-formyltetrahydrofolate or methotrexate. The preferred substrates for both binders appear to be the fully oxidized and partially reduced folates rather than the fully reduced folates. The lower-molecular-weight folate binding protein shows reversible binding with partially and fully reduced folates but irreversible binding with oxidized folates. This property suggests that this binder may have some function in the transport and storage of folate. The higher-molecular-weight folate binding protein, however, has only slight reversibility of binding with the partially and fully reduced folates, and it is therefore more difficult to postulate a physiologic function for this binding factor.
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PMID:The heterogeneity and properties of folate binding proteins from chronic myelogenous leukemia cells. 110 96

The A431 human epidermoid carcinoma cell line exhibits a 30-100-fold overexpression of the epidermal growth factor (EGF) receptor. We have characterized a membrane-associated phosphotyrosyl-protein phosphatase (PTPase) in these cells since it seemed reasonable that overexpression of the EGF-receptor tyrosine kinase will be matched by high PTPase activity. Indeed, of 12 cell lines tested, the A431 cells had the highest specific PTPase activity. About 70% of the total cellular PTPase activity was found associated with membranes after cell fractionation. The membrane-associated PTPase was hydrophobic as judged by its behaviour in Triton X-114 phase partitioning. High-performance liquid chromatography (HPLC) on a DEAE column revealed a single, homogeneous species of membrane-associated PTPase with an apparent molecular mass of 43 kDa as determined by HPLC on a gel permeation column in the presence of Triton X-100. Comparison of this PTPase with the membrane-associated PTPase activities present in rat spleen and in the human chronic myelogenous leukemia cell line K562 revealed additional species resolvable by DEAE-HPLC. These findings suggest that cells may possess different PTPase activities depending on their growth and differentiation states.
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PMID:Characterization of a membrane-associated phosphotyrosyl protein phosphatase from the A431 human epidermoid carcinoma cell line. 255 94

The metabolism of 6-mercaptopurine (6-MP) in L-1210 mouse leukemia cells and human chronic myelocytic leukemia cells (CML cells) was examined. The acid-soluble fractions obtained from cells incubated with [8-14C]6-MP were chromatographed on a Dowex-1 formate resin column using a formic acid linear gradient elution system. Chromatography of the extract of L-1210 cells revealed four principal radioactive peaks. The fraction containing the third peak was hydrolyzed by snake venom 5'-nucleotidase (Crotalus adamanteus). Cellulose thin layer chromatography revealed that the radioactive peak of the hydrolysate corresponded to 6-thioguanosine. The results showed that 6-MP was converted to 6-thioinosinic acid (6-TIMP) and 6-thioguanylic acid (6-TGMP) in L-1210 cells. In order to elucidate the pathway of 6-MP conversion to 6-TGMP, we examined the interaction of [8-14C]6-TIMP and purified IMP dehydrogenase. It was found by DEAE-cellulose thin layer chromatography that the IMP dehydrogenase converted 6-TIMP to 6-thioxanthylic acid (6-TXMP). Dowex-1 chromatography of the acid-soluble extract of human CML cells incubated with [8-14C]-6-MP also revealed a radioactive peak corresponding to 6-TGMP. These results suggest that 6-MP is metabolized to 6-TGMP by serial conversion to 6-TIMP and 6-TXMP through the de novo GMP synthetic pathway in L-1210 cells and human CML cells.
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PMID:Conversion of 6-mercaptopurine to 6-thioguanylic acid in L-1210 cells and human leukemia cells. 285 24


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