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)

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

The chronic myelogenous leukemia-associated P210 BCR-ABL oncogene protein product has been produced using the baculovirus expression system. High-level expression of the P210 BCR-ABL protein required the removal of GC rich 5' non-coding sequences. P210 BCR-ABL synthesized in insect cells is an active tyrosine protein kinase indistinguishable from P210 BCR-ABL isolated from human cells. Both proteins utilize angiotensin II as a phosphate acceptor in vitro with a Km for ATP of approximately 1.5 microM. P210 BCR-ABL produced in insect cells undergoes autophosphorylation in vitro and in vivo. Gel filtration of P210 BCR-ABL reveals that the protein elutes as a high molecular weight complex of about 800 kD. Approximately 4 to 5 mg of P210 BCR-ABL is produced in one liter of infected insect cells. Following cell disruption and a three-step ion exchange and gel filtration purification procedure, 0.4 mg of soluble P210 BCR-ABL is obtained per liter of suspension culture. An alternative procedure employing detergent extraction and immunoaffinity chromatography gave higher yields and purity from smaller amounts of infected cell extracts. The availability of intact, soluble and enzymatically active P210 BCR-ABL represents a significant advance for studying the biochemical and biophysical properties of the ABL oncogene family of proteins.
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PMID:Baculovirus expression of functional P210 BCR-ABL oncogene product. 249 63

Supernatants were prepared from short-duration explant cultures of term human placentas obtained after cesarean delivery. These supernatants inhibited murine and human mixed lymphocyte reactions, as well as CTL generation. The effects were reversed by an excess of IL-2-containing medium. Similarly, the material inhibited human natural killer cytotoxicity against K 562 targets. The material was subjected to gel-filtration chromatography on an ACA 44 or Bio-Gel A15m column. The apparent MW of the MLR-CML material was about 60-70 kDa, whereas the NK inhibiting activity was eluted in high-MW components (greater than 200 kDa) as well as in the 50-kDa range. The relevance of this material in local immunoregulation during human pregnancy is discussed.
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PMID:Immunoactive products of human placenta. I. An immunoregulatory factor obtained from explant cultures of human placenta inhibits CTL generation and cytotoxic effector activity. 252 22

The rapid synthesis of poly-gamma-glutamyl derivatives of 7-hydroxymethotrexate (7-OH-MTX) and their selective intracellular retention are reported in human chronic myelogenous leukemia cells, K-562. After a 30-min exposure to 5 microM [3H]7-OH-MTX, three different polyglutamyl derivatives were detected by high-performance liquid chromatography. When extracellular 7-OH-MTX was removed, the 7-OH-MTX diglutamate level declined slowly in comparison to the monoglutamate, but the higher polyglutamyl derivative levels increased. Within 10 min after exposure of cells to 7-OH-MTX, the level of these polyglutamyl derivatives far exceeds the dihydrofolate reductase binding capacity. Gel filtration or charcoal binding analysis followed by high-performance liquid chromatography analysis of the bound component showed intracellular binding of virtually all 7-OH-MTX tetraglutamate at a level 4-fold higher than that of the dihydrofolate reductase binding capacity. No bound 7-OH-MTX diglutamate or triglutamate could be detected. Treatment of the 7-OH-MTX tetraglutamate: protein complex with 100 microM unlabeled methotrexate (MTX) for 15 min resulted in only a partial dissociation of this complex to an extent compatible with the dihydrofolate reductase level. The residual 7-OH-MTX tetraglutamate remained bound to a site with a molecular weight of approximately 25,000 to 35,000 as assessed by Bio-Gel P-60 analysis and could not be displaced by folic acid, 5-formyltetrahydrofolate, 7-OH-MTX, or the tetraglutamate of MTX. 7-OH-MTX and MTX cytotoxicities were compared by clonogenic assay in agar and by their effects on cell growth. After a 2-hr exposure, the 50% inhibitory concentrations for 7-OH-MTX and MTX in cells growing in agar were 10(-5) and 10(-6) M, respectively. A 10-fold difference in cytotoxicity was also observed in cells growing in suspension. Continuous exposure to glycine: adenosine: thymidine completely protects cells from a sustained exposure to 7-OH-MTX over the entire period of clonal growth. However, even a brief exposure to 7-OH-MTX also requires continuous exposure to glycine: adenosine: thymidine for protection. This suggests that, as observed for MTX, the 7-OH-MTX polyglutamyl derivatives that are retained within the cells have a sustained cytotoxic effect after the monoglutamate is removed.
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PMID:Formation of 7-hydroxymethotrexate polyglutamyl derivatives and their cytotoxicity in human chronic myelogenous leukemia cells, in vitro. 257 1

Patient B. J. with chronic myelocytic leukemia excreted 0.5-1.1 g protein per day in the urine. Gel filtration on Sephadex G-75 showed about one-third of this protein to be in molecular weight range 20,000-40,000 (fraction BJC). BJC, prepared from 9 liters of urine by gel filtration, was chromatographed on carboxymethylcellulose. Two proteins were eluted from the resin in pure form (as shown by zone and immunoelectrophoresis) in yields representing 8 and 3 mg/liter of urine: BJC1 and BJC2. Their amino acid compositions were identical. BJC1 contained 61% carbohydrate (33% hexose, 11% sialic acid, 13% glucosamine, 5% galactosamine). BJC2 contained one-fourth to one-half as much of each carbohydrate. Molecular weight of BJC1 was estimated at 29,000 by gel filtration. Neither glycoprotein reacted with rabbit antiserum to normal human serum.Antiserum to BJC1 was made in the rabbit. Immunoelectrophoresis with this antiserum showed a faint precipitin line, corresponding in mobility to BJC1, in normal human plasma, and a stronger line in most leukemic plasmas. By immunodiffusion, BJC1 was not detectable in normal human urine, but a positive reaction occurred in the following conditions: leukemia, 64-72%; other types of disseminated neoplastic disease, 36-78%; regional ileitis, 45%; ulcerative colitis, 38%; tuberculosis, 33%; during the 1st wk after major surgery, 33%.BJC2 was found in the urine by immunoelectrophoresis in 10% of patients with neoplastic disease and was not observed in urine of other patients or in human plasma. Amino acid composition, carbohydrate content, and antigenic specificity indicate BJC1 is a previously unrecognized member of the system of normal human plasma glycoproteins. Like certain other glycoproteins, its plasma concentration frequently increases in patients with neoplastic disease, chronic inflammatory disease, or tuberculosis and after surgery. Because molecular weight is 29,000, increased plasma concentration readily causes its appearance in the urine.
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PMID:Isolation of a novel glycoprotein from the urine of a patient with chronic myelocytic leukemia. 420 83

Peripheral blood granulocytes from patients with chronic myelogenous leukemia (CML) were studied for accessibility of membrane sialic acid and galactose residues to sodium borohydride-3H radiolabeling after oxidation with sodium metaperiodate (PI/B3H4) or with galactose oxidase (GO/B3H4). Granulocytes from untreated patients with chronic myelogenous leukemia showed increased radiolabeling with PI/B3H4, and decreased labeling with GO/B3H4 when compared to normal granulocytes. Granulocytes from leukemic patients receiving chemotherapy showed normal labeling patterns. Gel electrophoresis of membrane extracts showed that the changes in PI/B3H4 and GO/B3H4 reactivity of CML cells were distributed over all membrane protein bands. Our data suggest that CML granulocyte membrane proteins are aberrantly sialylated, with decreased accessibility of galactose residues, and that these changes may be reversed by clinical drug treatment.
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PMID:Aberrant sialylation of granulocyte membranes in chronic myelogenous leukemia. 658 35

The 37 K protein, earlier found to be present in 3.75% PEG-precipitates from sera of untreated patients with CML, was further characterized. Gel filtration at neutral pH resolved the PEG-precipitate into a non-IgG containing protein peak-I and a IgG containing peak-II. Immunoprecipitation of peak-II with antihuman IgG antiglobulin and subsequent 2D-SDS-PAGE analysis of the immunoprecipitate revealed the presence of 37 K protein in peak-II confirming its association with IgG. 125I-37 K protein was found to interact with antibodies isolated from autologous and allogenic CML-CIC samples but not with similarly isolated antibodies from normal subject, and patients with AML, ALL, MF, and HD. Peptide maps generated by tryptic digestion of 37 K protein (from five different CML patients) were found to be identical. Specific interaction of 37 K protein with the autologous and allogenic antibodies and identity of peptide maps lead to the conclusion that the 37 K protein is a CML-associated antigen appearing in CIC.
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PMID:Circulating immune complexes in chronic myeloid leukemia: studies on 37 K protein antigen. 659 85

Particulate membrane preparations from K-562 [human CML (chronic-myelogenous-leukaemia)-derived] cells catalyse the transfer of [3H]galactose from UDP-[3H]-galactose and [3H]N-acetylglucosamine from UDP-[3H]N-acetylglucosamine into an endogenous product that on digestion with Pronase yields long-chain glycopeptides (mol.wt. 7000--10 000) called 'erythroglycan'. Incorporation of either labelled sugar increased up to 60 min of incubation time. The labelled erythroglycan was isolated by chromatography on Sephadex G-50 and characterized by digestion with endo-beta-galactosidase from Escherichia freundii, followed by analysis on Bio-Gel P-2 and paper chromatography. This digestion gave the following four products: (1) a disaccharide with the sequence beta GlcNAc-beta Gal; (2) a trisaccharide with the sequence betaGal-betaGlcNAc-beta Gal; (3) a larger oligosaccharide containing galactose and N-acetylglucosamine; and (4) a putative protein-linkage region.
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PMID:Cell-free biosynthesis of erythroglycan in a microsomal fraction from K-562 cells. 679 62

Advanced glycation end products (AGEs) and glycoxidation products are formed during Maillard or browning reactions between sugars and proteins and are implicated in the pathophysiology of aging and the complications of diabetes. To determine the structure of AGEs, antibodies were prepared to protein browned by incubation with glucose and used in ELISA assays to measure AGEs formed in model reactions between bovine serum albumin (BSA) or N alpha-acetyllysine and glucose, fructose, or glyoxal. AGEs were formed from glucose and fructose only under oxidative conditions, but from glyoxal under both oxidative and antioxidative conditions. Gel permeation chromatographic analysis indicated that a similar AGE was formed in reactions of N alpha-acetyllysine with glucose, fructose, and glyoxal and that this AGE co-eluted with authentic N alpha-acetyl-N epsilon-(carboxymethyl)lysine. Amino acid analysis of AGE proteins revealed a significant content of N epsilon-(carboxymethyl)lysine (CML). In ELISA assays using polyclonal antibodies against AGE proteins, CML-BSA (approximately 25 mol of CML/mol of BSA), prepared by chemical modification of BSA, was a potent inhibitor of the recognition of AGE proteins and of AGEs in human lens proteins. We conclude that AGEs are largely glycoxidation products and that CML is a major AGE recognized in tissue proteins by polyclonal antibodies to AGE proteins.
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PMID:N epsilon-(carboxymethyl)lysine is a dominant advanced glycation end product (AGE) antigen in tissue proteins. 766 68

A reciprocal translocation between chromosomes 9 and 22 creates the Philadelphia (Ph1) chromosome in chronic myelogenous leukemia. This translocation results in the fusion of the ABL and the BCR genes to form a BCR/ABL fusion gene, the product of which has a greatly increased protein tyrosine kinase activity in comparison with the normal ABL protein. The chromosome 22 translocation breakpoints are concentrated within a 5.8-kilobase region named the major break-point cluster region (Mbcr). Gel mobility shift and DNase I footprinting assays have defined binding sites for three proteins, BIF 1-3 (BCR intron factors 1-3), lying within a 427-base pair fragment of the Mbcr. This 427-base pair fragment functions as a transcriptional silencer with both the BCR as well as a heterologous promoter. The silencing is position- and orientation-independent. The transcriptional effects are greatest in chronic myelogenous leukemia cells, decreased in HeLa and B-cells, and absent in T-lymphocytes. Gel mobility shift assays show a corresponding difference in pattern when the T-lymphocyte nuclear extract is compared with other cell lines. The Mbcr appears to contain a novel group of transcriptional silencers that share a common binding motif with a recently described suppressor in the mouse Adh-1 gene.
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PMID:A novel transcriptional suppressor located within a downstream intron of the BCR gene. 814 70


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