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)

In three experiments, activity of hepatic enzymes associated with metabolism of methionine through the transulfuration pathway were studied with respect to possible effects of diet and methionine infusion per abomasum. In experiment 1 no differences in methionine adenosyltransferase (MAT) or cystathionine lambda-lyase (CGL) were detected between lucerne and wheaten straw diets, or between effects of fasting for 48 h and 96 h after feeding lucrene chaff as opposed to fasting after feeding wheaten straw. Fasting for 96 h resulted in a trend toward increasing CGL and MAT specific activities on both diets. In experiment 2 MAT was depressed significantly by infusion of methionine at 1.4 g/day and to a greater extent by infusion at 4.2 g/day, whilst CGL was not significantly affected. In experiment 3 MAT specific activity decreased significantly in response to both levels of methionine supplementation. Betaine-homocysteine methyltransferase activity was increased by methionine infusion. CGL decreased in all treatments but there was a larger decrease in those animals receiving methionine infusion. No significant changes were observed in relation to other enzymes examined which included cystathionine beta-synthase and threonine dehydratase. These observations are consistent with the hypothesis that in sheep the increase in methionine in blood plasma which occurs when methionine is absorbed in increased amounts may be due to reduced entry into the transulfuration pathway because of a repression of MAT activity.
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PMID:The effect of diet and of methionine loading on activity of enzymes in the transulfuration pathway in sheep. 67 17

Recent data suggest that basophils express receptors for a variety of lymphokines. In this study we present the biochemical characterization of the interleukin-2 (IL-2) receptor on the basophil surface membrane. Highly enriched populations (purity: 92% to 99%) of blood basophils were obtained from chronic granulocytic leukemia (CGL) patients (n = 3) by negative selection using monoclonal antibodies (MoAbs) and complement. CGL basophils were found to bind CD25 MoAbs (n = 4) directed against different epitopes of the 55- to 60-Kd subunit of the IL-2 receptor (= Tac peptide). Immunoprecipitation experiments with lysates of purified CGL basophils and CD25 MoAbs showed a protein with a molecular weight of 60 Kd, equivalent to the Tac peptide on human T blasts. Quantitative binding studies and Scatchard plot analysis using radiolabeled recombinant human (rh) IL-2 indicated the presence of 12,000 +/- 4,700 low affinity IL-2 binding sites (kd = 66 nmol/L) per purified CGL basophil. Northern blot analysis with enriched CGL basophils showed two messenger RNA bands of 3.5 and 1.5 kilobases hybridizing to radiolabeled Tac cDNA. Immunoprecipitation of the Tac peptide from enriched basophils metabolically labeled with 35S-methionine showed active synthesis of the IL-2 receptor. Our results show that human blood basophils synthesize and express receptors for IL-2.
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PMID:Human blood basophils synthesize interleukin-2 binding sites. 169 35

Glycoprotein Ib (GPIb), the receptor for von Willebrand factor, is a two-chain member constituent of the platelet/megakaryocytic lineage. Studies on its expression have been hampered by the difficulties in obtaining purified megakaryocytes in a sufficient number. We report a suspension liquid culture procedure that allowed isolation of more than 1 x 10(6) megakaryocytes with a purity ranging from 3% to 88% from the blood of patients with chronic myeloid leukemia, from fetal liver or from normal human bone marrow. GPIb was detected on the plasma membrane of all maturing megakaryocytes and also of promegakaryoblasts devoid of demarcation membranes. GPIb was detected on demarcation membranes of maturing megakaryocytes but was absent from all other organelles, including alpha granules. Biosynthesis of 35S-methionine labeled megakaryocytes showed that GPIb with similar electrophoretic mobility to the platelet molecule was synthesized and that it was also composed of two chains, since its molecular weight shifted in reducing conditions from 170 Kd to 145 Kd. The beta chain remained undetectable after methionine metabolic labeling, but it was immunoprecipitated after 3H-leucine metabolic labeling, confirming that this subunit is devoid of methionine. GPIb was associated with GPIX, as it is in platelets, since anti-GPIb antibodies coprecipitated a 17 Kd polypeptide.
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PMID:Expression of platelet glycoprotein Ib by cultured human megakaryocytes: ultrastructural localization and biosynthesis. 219 92

CML cell line, KU-812-F, originally established from a patient with Philadelphia-chromosome-positive chronic myelocytic leukemia has maintained the ability to differentiate into both granuloid (basophilic) and erythroid lineages. The expression of P210bcr/abl in KU-812-F cells during differentiation was studied by immunoblotting and immunoprecipitation. Immunoblotting with anti-phosphotyrosine sera revealed the down-regulation of P210bcr/abl in both granuloid and erythroid lineages. Immunoprecipitation with anti-abl antibodies of 35S-methionine-labelled cells revealed a reduced rate of synthesis of P210bcr/abl protein. Cytotoxic agents that caused growth inhibition of the cells did not alter the expression of P210bcr/abl. These results indicate that the down regulation of P210bcr/abl protein is a lineage non-specific event accompanied by differentiation.
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PMID:Lineage non-specific down regulation of P210bcr/abl in the CML cell line, KU-812-F, during differentiation. 223 52

Immunofluorescence staining of buffy coat smears from a patient with chronic myelogenous leukemia in accelerated phase showed that approximately 13% of all nucleated cells contained von Willebrand protein and, therefore, appeared to be of megakaryocytic origin. This was confirmed by positive staining with antisera against platelet factor 4 and platelet glycoproteins. Short-term cultures of the buffy coat, which lacked endothelial cells, were metabolically labeled with [35S]methionine, and von Willebrand protein was immunopurified from cell lysates and culture medium. Cultures from this patient synthesized and secreted von Willebrand protein, in contrast with cultures from other patients with leukemia, who lacked circulating megakaryocytes, and from normal volunteers. The subunit composition of the megakaryocytic von Willebrand protein was very similar to that of human umbilical vein endothelial cells. The size of the processed subunit (220 kD) and of the cellular (260 kD) and secreted (275 kD) precursors from the two cell types were indistinguishable by gel electrophoresis. Furthermore, the ratio of precursor to processed subunit and the pattern of cellular and secreted nonreduced multimers were very similar. It appears, therefore, that the processing steps in biosynthesis of von Willebrand protein used by the megakaryocytes are very similar to those of umbilical vein endothelial cells.
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PMID:Biosynthesis of von Willebrand protein by human megakaryocytes. 241 71

Human chronic myelogenous leukemia is characterized by a reciprocal translocation between chromosomes 9 and 22. This results in the transfer of the c-abl protooncogene from chromosome 9 into the bcr gene on chromosome 22. The purpose of this study was to characterize the bcr and related gene products. Antibodies were raised against a fused trpE-bcr protein induced in a bacterial expression vector. Immunoprecipitation with the monoclonal and polyclonal antibodies of metabolically [35S]methionine labeled leukemic cell lines shows a 210, 160 and 130 Kda protein in Philadelphia positive cells containing the bcr-abl fused transcript. Only the 160 and 130 Kda were present in the Philadelphia negative cells. In vitro kinase assay shows that the 130 Kda protein is a phosphoprotein mainly phosphorylated on serine. Partial proteolysis indicates that the p210 and p130 share common domains. In subcellular fractionation experiments, the p130 is colocalized with the p210 bcr-abl in the cytoplasmic fraction. Together with the mapping of 4 distinct bcr related loci our data suggest that the 130 Kda phosphoprotein belongs to a wider family of bcr related gene products.
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PMID:Identification of a 130 Kda bcr related gene product. 249 32

The bcr gene plays a critical role in the pathogenesis of two human leukemias associated with the Philadelphia chromosome: chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). In both instances a chimeric gene, formed between bcr and the abl protooncogene, results in expression of fused bcr-abl proteins with tyrosine kinase activity. There is controversy regarding the normal gene products of bcr. We investigated this problem by several techniques and found proteins of 190/185, 155, 135, 125, 108, 83 and 47 kDa in several human cell lines by immunoprecipitation with two distinct site-directed anti-bcr antibodies termed anti-bcr(738-753) and anti-bcr(898-911). The 190/185, 155, 125 and 108 kDa proteins were consistently detected by anti-bcr(898-911) antibodies by immunoblotting. Antibodies pre-reacted with excess bcr peptide did not detect these proteins. These proteins were labeled with [32P]orthophosphate in vivo and in vitro by [gamma 32P]ATP in immune complex kinase assays performed with anti-bcr antibodies indicating that these proteins are phosphorproteins. Following labeling in kinase assays, phosphoamino acid analyses detected both phosphoserine and phosphothreonine. In structural studies using one dimensional peptide maps derived by partial V8 protease treatment, the 185, 155, 135, 125 and 108 kDa proteins shared several peptide fragments but contained unique fragments as well. Similarly 2-dimensional maps of proteins labeled in the kinase assay exhaustively digested with trypsin, revealed homology between the 155, 135, 125, 108, and 83 kDa proteins. bcr proteins sedimented in glycerol gradients as putative complexes detected in the cytoplasm of the cell. A 47 kDa protein as well as the recently identified Ph-P53 protein appeared to be associated with bcr proteins based on their co-sedimentation in glycerol gradients and co-immunoprecipitation with several different anti-bcr antibodies. None of the proteins exhibited a precursor-product relationship in pulse-chase experiments conducted with [35S]methionine. We conclude that human cells express several different bcr gene products ranging in size from 190 to 83 kDa, and that these proteins can form specific intracellular cytoplasmic complexes with other cellular proteins.
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PMID:Characterization of bcr gene products in hematopoietic cells. 264 52

Platelet membrane glycoprotein IIb-IIIa forms a calcium-dependent heterodimer and constitutes the fibrinogen receptor on stimulated platelets. GPIIb is a two-chain protein containing disulfide-linked alpha and beta subunits. GPIIIa is a single chain protein. These proteins are synthesized in the bone marrow by megakaryocytes, but the study of their synthesis has been hampered by the difficulty in obtaining enriched population of megakaryocytes in large numbers. To examine the biosynthesis and processing of GPIIb-IIIa, purified human megakaryocytes were isolated from liquid cultures of cryopreserved leukocytes stem cell concentrates from patients with chronic myelogenous leukemia. Immunoprecipitation of [35S]methionine pulse-chase-labeled cell extracts by antibodies specific for the alpha or beta subunits of GPIIb indicated that GPIIb was derived from a precursor of Mr 130,000 that contains the alpha and beta subunits. This precursor was converted to GPIIb with a half-life of 4-5 h. No precursor form of GPIIIa was detected. The glycosylation of GPIIb-IIIa was examined in megakaryocytes by metabolic labeling in the presence of tunicamycin, monensin, or treatment with endoglycosidase H. The polypeptide backbones of the GPIIb and the GPIIIa have molecular masses of 120 and 90 kD, respectively. High-mannose oligosaccharides are added to these polypeptide backbones co-translationally. The GPIIb precursor is then processed with conversion of high-mannose to complex type carbohydrates yielding the mature subunits GPIIb alpha (Mr 116,000) and GPIIb beta (Mr 25,000). No posttranslational processing of GPIIIa was detected.
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PMID:Biosynthesis and processing of platelet GPIIb-IIIa in human megakaryocytes. 310 66

We have previously described the detection and partial characterization of a common myelogenous leukemia-associated antigen (CAMAL), in CGL and ANLL patients. Both polyclonal and monoclonal (CAMAL-1) antibodies have been raised to p70 (CAMAL) and have been shown to react with both p70 and myeloid leukemia cell preparations. p70 (CAMAL) has been shown to be a monomeric protein of Mr 70,000 and pI 7.2 and was also detectable in the myeloid leukemia cell lines HL60, KG1, K562 and U937, but not in the lymphocytic cell lines Molt-4, Hut-78 and CEM by immunoprecipitation from iodinated cell samples. Using [35S] methionine-labeled cell lines and immunoprecipitation, we have demonstrated the constitutive expression of p70 as well as a major component at p58 and a number at lower molecular weights in the myeloid leukemia cell lines HL60, KG1, K562 and U937, but not in the lymphocytic leukemia cell lines Molt-4, Hut-78 and CEM. The implications of these observations are discussed.
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PMID:Expression of a leukemia-associated antigen (CAMAL) in four myeloid leukemia cell lines. 317 16

The Philadelphia chromosome (Ph1), observed in greater than 90% of chronic myelogenous leukemia (CML) patients, results from a specific chromosomal translocation involving the c-abl gene. The translocation breakpoint occurs near c-abl and correlates with the production of an altered c-abl mRNA. In the CML-derived cell line K562, Ph1 is accompanied by a structurally altered c-abl protein (P210c-abl) with in vitro tyrosine kinase activity not detected with the normal c-abl protein (P145c-abl). We have examined c-abl proteins in other Ph1-positive CML cell lines and found that they all express P210c-abl. P210c-abl was also detected in bone marrow cells from CML patients with Ph1 in the accelerated and blast crisis phases of the disease. Comparison of the [35S]methionine-labeled tryptic peptides generated from the normal P145c-abl and P210c-abl showed that they have closely related structures, but additional polypeptide sequences are present in P210c-abl. Based on these results we propose that translocation of c-abl in Ph1-positive CML results in the creation of a chimeric gene leading to the production of a structurally altered c-abl protein with activated tyrosine kinase activity. The altered P210 c-abl protein is strongly implicated in the pathogenesis of CML.
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PMID:Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. 385 62


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