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

The processing and intracellular transport of lactoferrin of the neutrophil specific granules was investigated by biosynthetic labeling with (14C)leucine of bone marrow cells from healthy individuals and patients with chronic myeloid leukemia. Lactoferrin was precipitated with antilactoferrin serum and the immunoprecipitates were analyzed by sodium dodecyl sulfate (SDS), polyacrylamide gel electrophoresis (PAGE) followed by fluorography. In contrast to myeloperoxidase of azurophil granules, lactoferrin was not synthesized as a larger precursor, and it was not found to be phosphorylated. The transfer to granules of newly synthesized lactoferrin was demonstrated in pulse-chase labeling experiments followed by centrifugation of cell homogenate in a Percoll gradient. Monensin, which exchanges protons for Na+ and NH4+ cation, blocked the transfer completely, indicating a need for acidification mechanisms. Unlike myeloperoxidase, newly synthesized lactoferrin rapidly became resistant to endoglycosidase H, indicating a transport through the medial and transcisternae of the Golgi apparatus with conversion of "high mannose" to "complex" oligosaccharide side chains. Intracellular transfer of some major neutrophil azurophil and specific granule constituents is obviously regulated differently. Lactoferrin seems to be processed like proteins destined for secretion, while myeloperoxidase is processed more or less like lysosomal enzymes.
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PMID:Biosynthesis and processing of lactoferrin in bone marrow cells, a comparison with processing of myeloperoxidase. 282 14

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

Two major lysosomal membrane glycoproteins with apparent Mr approximately 120,000 were purified from chronic myelogenous leukemia cells. These glycoproteins are major sialoglycoproteins containing polylactosaminoglycan and represent approximately 0.1-0.2% of total cell proteins. A monoclonal antibody specific to one of the glycoproteins and polyclonal antibodies specific to the other glycoprotein were obtained. Immunoelectron microscopic examination of HeLa cells revealed that these two glycoproteins mainly reside in lysosomes and multivesicular bodies. Immunoprecipitation experiments showed that a number of different cell lines express these glycoproteins. However, the apparent molecular weights differed between cell lines; this probably represents differences in the amount of polylactosaminoglycan expressed by each cell line. As shown in the following paper (Fukuda, M., Viitala, J., Matteson, J., and Carlsson, S. R. (1988) J. Biol. Chem. 263, 18920-18928) one of the glycoproteins is very homologous to that of a mouse counterpart, m-lamp-1. The human form of this glycoprotein is therefore named human lamp-1 (h-lamp-1), while the other glycoprotein, to which the monoclonal antibody was made, is called human lamp-2 (h-lamp-2). Pulse-chase labeling experiments detected that h-lamp-1 and h-lamp-2 are produced first as precursor forms of 87.5 and 84 kDa, and treatment with endo-beta-N-acetylglucosaminidase H (endo-H) or endo-beta-N-acetylglucosaminidase F (endo-F) reduced their molecular masses to 39.5 and 41.5 kDa, respectively. It was estimated that h-lamp-1 has 18 N-linked saccharides and h-lamp-2 16, based on the results of partial digestions with endo-F. These results indicate that the two lysosomal membrane glycoproteins are extensively modified by N-glycans, and some of these were found to have polylactosaminyl repeats and sialic acid. Human lamp-1 and lamp-2, therefore, serve as good models for understanding polylactosaminoglycan formation and the biosynthesis and processing of polylactosaminoglycan-containing glycoprotein.
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PMID:Isolation and characterization of human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Major sialoglycoproteins carrying polylactosaminoglycan. 314 19

Lysosomal arylsulfatases A and B of peripheral leukocytes from patients with chronic myelogenous leukemia and from healthy subjects were studied. Two enzyme activities of leukemia cells were significantly higher than those of cells from healthy subjects, irrespective of total and differential counts of leukemic cells. Upon anion-exchange chromatography, the arylsulfatases of chronic myelogenous leukemia cells and normal leukocytes were separated into the basic B enzyme and its anionic variant (B1) and A enzyme. However, the amount of B1 enzyme relative to B enzyme or the activity ratio of B1 enzyme to total arylsulfatase B (B + B1) was higher in chronic myelogenous leukemia cells than in normal cells. The anionic property of the enzyme was found to be due to phosphate groups bound to the carbohydrate moiety of the arylsulfatase, based on the following results. When B1 enzyme was treated with alkaline phosphatase followed by isoelectric focusing, it was changed to a less anionic enzyme with heterogeneous components which are ascribed to phosphodiester groups linked to the heterogeneous carbohydrate moiety of the enzyme; no effect was observed by sialidase treatment. Upon treatment of B1 enzyme with endo-beta-N-acetylglucosaminidase H, which cleaves sugar chains of a high mannose type in glycoproteins, the anionic heterogeneous components were converted to the basic component similar to B enzyme. From our present and previous observations, it can be concluded that the increase of phosphorylated forms of the lysosomal hydrolase represents one characteristic of rapidly proliferating neoplastic cells.
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PMID:Lysosomal arylsulfatases of human leukocytes: increment of phosphorylated B variants in chronic myelogenous leukemia. 613 78