Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse myeloma immunoglobulin IgM heavy chains were cleaved with cyanogen bromide into nine peptide fragments, four of which contain asparagine-linked glycosylation. Three glycopeptides contain a single site, including Asn 171, 402, and 563 in the intact heavy chain. Another glycopeptide contains two sites at Asn 332 and 364. The carbohydrate containing fragments were treated with Pronase and fractionated by elution through Bio-Gel P-6. The major glycopeptides from each site were analyzed by 500 MHz 1H-NMR and the carbohydrate compositions determined by gas-liquid chromatography. The oligosaccharide located at Asn 171 is a biantennary complex and is highly sialylated. The amount of sialic acid varies, and some oligosaccharides contain alpha 1,3-galactose linked to the terminal beta 1,4-galactose. The oligosaccharides at Asn 332, Asn 364, an Asn 402 are all triantennary and are nearly completely sialylated on two branches and partially sialylated on the triantennary branch linked beta 1,4 to the core mannose. The latter is sialylated about 40% of the time for all three glycosylation sites. The major oligosaccharide located at Asn 563 is of the high mannose type. The 1H-NMR determination of structures at Asn 563 suggests that the high mannose oligosaccharide contains only three mannose residues.
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PMID:Major carbohydrate structures at five glycosylation sites on murine IgM determined by high resolution 1H-NMR spectroscopy. 408 5

Approximately 15 per cent of the light chains from homogeneous immunoglobulins in patients with multiple myeloma contain an oligosaccharide group. Five human myeloma light chains that contained carbohydrate were studied. The sequence Asn-[unk]-Ser/Thr was at the site of carbohydrate attachment in all light chains. The carbohydrate group was attached to the asparagine residue of this triplet sequence which in all five light chains was located in the variable region. The occasional occurrence of carbohydrate in myeloma light chains is seen as the consequence of a variable region mutation creating an Asn-[unk]-Ser/Thr sequence to which carbohydrate is attached by an enzyme capable of recognizing the characteristic triplet sequence.
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PMID:Attachment of carbohydrate to the variable region of myeloma immunoglobulin light chains. 419 90

Forty-two human hematopoietic cell lines were assessed for sensitivity to a four-day incubation with L-asparaginase. Eight of 13 T-leukemia cell lines and 1 of 7 non-T, non-B common acute lymphoblastic leukemia cell lines exhibited an ID50 (50% growth inhibition dose) of less than 0.0001 IU/ml. Seven of these sensitive cell lines were further cultured in L-asparagine-free medium and were found not to proliferate. Five T-leukemia cell lines, 6 non-T, non-B common acute lymphoblastic leukemia cell lines, 10 "abnormal" B-cell lines, 4 "normal" B-cell lines, 3 myeloma cell lines and 5 myeloid leukemia cell lines had ID50 values between 0.1 and 1.0 IU/ml. Twelve of these resistant cell lines were able to proliferate in L-asparagine-depleted medium. The results indicate that some patients with T-cell acute lymphoblastic leukemia might respond to this enzymatic antineoplastic drug, L-asparaginase, at low dose.
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PMID:Distinctive sensitivity of some T-leukemia cell lines to L-asparaginase. 660 60

The complete amino acid sequence of the human myeloma IgD:WAH has been determined and the sites of asparagine glycosylation identified as residues 354, 445, and 496 (Takahashi, N., Tetaert, D., Debuiere, B., Lin, L.-C., and Putnam, F. W. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 2850-2854). We have determined the structures of the oligosaccharides at each of these positions. Asn 354 bears oligosaccharides exclusively of the high mannose type containing from 5 to 9 mannose residues. Twenty per cent of the oligosaccharides at this site contain 1 glucose residue at the terminus of the branch emanating from the alpha 1 leads to 3-linked core mannose which is believed to reflect incomplete processing of the triglucosyl-high mannose oligosaccharide intermediate following transfer from dolichol to nascent peptide. Asn 445 and Asn 496 bear exclusively dibranched complex oligosaccharide structures; 30-40% of these molecules contain a bisecting GlcNAc-linked beta 1 leads to 4 to the innermost core mannose residue. At Asn 445, 40% of both the bisected and nonbisected oligosaccharides contain 1 residue of fucose on the Asn-linked GlcNAc and 50% bear a single N-acetylneuraminic acid residue. The oligosaccharides at Asn 496 are devoid of sialic acid and fucose. Thus, IgD:WAH is notable for the presence of virtually unprocessed oligosaccharide structures (glucosylated high mannose) on the same peptide backbone as extensively processed complex type molecules. The finding that each of the 3 Asn glycosylation sites of IgD:WAH bears either exclusively a complex or a high mannose type oligosaccharide indicates that there is considerable specificity in the glycosylation process. These oligosaccharides, nonetheless, display extensive microheterogeneity at each location.
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PMID:Structures of the oligosaccharides present at the three asparagine-linked glycosylation sites of human IgD. 661 27

In the previous communication (Mellis, S. J., and Baenziger, J. U. (1983) J. Biol. Chem. 258, 11546-11556), the structures of the oligosaccharides present at the 3 asparagine glycosylation sites of a human IgD myeloma protein were defined. In this communication, we present the structures of the O-glycosidically linked oligosaccharides located in the hinge region of IgD:WAH. Three or four threonine residues and one serine residue in the region bear O-glycosidically linked oligosaccharides. Approximately 50% of these molecules have the structure Gal beta 1 leads to 3 GalNAc which is identical with the structure of the predominant oligosaccharide in the hinge region of human IgA1 myeloma proteins (Baenziger, J. U., and Kornfeld, S. (1974) J. Biol. Chem. 249, 7270-7281). The remainder of the oligosaccharides contain 1 or 2 residues of N-acetylneuraminic acid and have the structures NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc (30%), Gal beta 1 leads to (NeuAc alpha 2 leads to 6)GalNAc (12%), and NeuAc alpha 2 leads to 3Gal beta 1 leads to 3(NeuAc alpha 2 leads to 6)GalNAc (8%). The sialylated molecules have not been encountered previously on other human immunoglobulin heavy chains. These structures, however, have been described on a number of secreted and membrane glycoproteins. Examination of oligosaccharides isolated from different subregions of the IgD hinge indicated that a specific distribution of the sialylated structures among the glycosylated amino acids of the hinge region is not likely.
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PMID:Structures of the O-glycosidically linked oligosaccharides of human IgD. 661 28

The complete amino acid sequence of an Fc-like fragment designated Fc delta (t) and obtained by limited proteolysis with trypsin of an intact myeloma IgD protein (NIG-65) has been determined. The fragment contains 226 amino acid residues and has a molecular weight of 32,000 per monomeric unit. It has three glucosamine oligosaccharides at asparagine residues 68, 159, and 210. Of these, glucosamine-159 is characteristic of the delta chain and has no counterpart position in any of the other classes. On the other hand, glucosamine-68 is shared by gamma, mu, and epsilon, and glucosamine-210 is shared by alpha and mu. Although the Fc delta (t) has the common framework structure of immunoglobulins, its sequence has many individual characteristics when its two domains are compared separately with the counterpart domain of other heavy chains. Such comparison has shown that the two Fc domains of the delta chain should be placed in an independent branch in topology; for all the other classes, the Fc domains are paired well with their counterparts. The comparison has also shown that there are three prominent gaps by which each domain can be divided into two homologous halves. For each class of immunoglobulin, a moderate degree of internal homology exists between the first half and the second half of each domain of the Fc, suggesting that the primordial gene may have coded for a unit about the size of a half domain. Based on this observation together with sequence comparisons, a possible genetic mechanism is proposed for the origin and evolution of the genes for immunoglobulin domains.
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PMID:Complete amino acid sequence of the Fc region of a human delta chain. 678 54

Mouse myeloma immunoglobulin IgM heavy chains were cleaved with cyanogen bromide into nine peptide fragments, four of which contain asparagine-linked sites of glycosylation. Three of these glycopeptides contain a single site located at asparagines 171, 403, and 563 in the sequence of the intact heavy chain. Another glycopeptide contains two sites of glycosylation at asparagines 332 and 364. All sites contain multiple oligosaccharide structures with a trend towards increased processing from the COOH to the NH2 terminus. Structures present at asparagine 563, located only exclusively high mannose oligosaccharides. Asparagine 403, located penultimate to the COOH terminus, has a major component that is of a complex nature but is incompletely processed. Other sites contain predominantly complex structures consisting of biantennary or triantennary branches. The unusual structure found at asparagine 403 contains fucose even though only one branch has been processed to a terminal galactose. These studies suggest that each site has a unique set of heterogeneous oligosaccharides derived from a complex processing system which utilizes a combination of "position completeness" and polypeptide structure to determine final carbohydrate structure.
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PMID:Heterogeneity of asparagine-linked oligosaccharides of five glycosylation sites on immunoglobulin M heavy chain from mineral oil plasmacytoma 104E. 681

We have cloned and sequenced cDNAs encoding the variable regions of the light (VL) and heavy (VH) chains of monoclonal antibody KC4G3. VL belongs to group II and resulted from a V kappa-J kappa 2 recombination. VH belongs to group IIId and arose from a V-D9-JH3 recombination. The VL and VH frameworks are respectively 84% and 83% identical to the corresponding VL and VH human consensus frameworks. The deduced amino acid sequence of VL contains an asparagine-linked glycosylation site in framework 3 (N74 I75 S76). We have determined that a large fraction of the light chains are indeed glycolysated. We constructed an IgG1, kappa human/mouse chimeric antibody (by inserting the murine KC4G3 Fv-encoding cDNAs into plasmids encoding a human IgG1, kappa Fc domain) and expressed it in SP2/0-Ag14 mouse myeloma cells. This chimeric monoclonal antibody is designated ChiKC4. We have determined that the murine monoclonal antibody KC4G3 binds the human breast mucin with an affinity constant of 1.1 x 10(9) M-1. ChiKC4 binds the same antigen with an affinity constant of 1.2 x 10(9) M-1. ChiKC4 binds the carcinoma tissue sections by the ABC immunoperoxidase method in an identical manner as does KC4G3.
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PMID:Cloning of cDNAs encoding the variable domains of antibody KC4G3 and construction of a chimeric antibody. 824 20

L-asparaginase is an enzyme which hydrolyses asparagine. Since the 1960s it has been known that some leukemic cells are deficient in asparagine synthetase and therefore cannot manufacture sufficient quantities of this essential amino acid to maintain cell viability. L-asparaginase is predominantly useful in acute lymphocytic leukemia (ALL) although responses have been noted in patients with acute myeloid leukemia, lymphoma, and rarely other tumors. L-asparaginase has been used in conjunction with methotrexate and ara-C in combination programs in leukemia. The major side-effect limiting the usefulness of L-asparaginase is allergic reactions. In addition, it is probable that neutralizing antibodies develop which shorten the half life of the drug so that the goal of depletion of plasma levels of asparagine cannot be attained or maintained. Polyethylene glycol (M.W. 5000) can be conjugated to L-asparaginase at sites not involving the active site of the enzyme. This enables free access of a small molecule, asparagine, to the active site of the enzyme but prevents uptake by the reticuloendothelial system, greatly decreasing the probability of developing antibodies against the asparaginase and prolongs the circulating half life of the drug. In a phase I/II study conducted at the M.D. Anderson Cancer Center, 37 heavily pretreated patients with refractory hematologic malignancy were treated. The age range from 15 to 73 years, median 49 years. Nineteen patients had ALL, 15 lymphoma, two myeloma, and one Hodgkin's disease. The dose levels of PEG L-asparaginase varied from 250 IU/m2 up to 8000 IU/m2. The pharmacokinetic profile demonstrated a monophasic half life consistent with a one compartment model with a single elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-asparaginase and PEG asparaginase--past, present, and future. 848 65

In a woman suffering from IgE myeloma, hay fever and polyvalent respiratory and skin allergy the IgE monoclonal protein VL was isolated and investigated with respect to structural and functional properties. The amino acid sequence of 22 isolated peptides--especially of the biologically significant C2-C3 part--corresponded with that originally described by Bennich et al. (Immunol Rev 1978;41:3-23; Prog Immunol 1974;13:49-58). However, in mass spectrometry the sugar residues on ASN 99 (219) and 252 (371) were deficient in sialic acids. The native IgE VL protein precipitated with high intensity all mannose-specific lectins as concanavalin A (Con A) and was able to release histamine after triggering by these lectins. The same lectins also elicited more histamine release and more positive skin reactions in atopic than in healthy persons. In sera from atopic patients the binding of IgE on Con A Sepharose 4B column was stronger than in normal persons. It is suggested that changes in the IgE glycosylation state may contribute to IgE-mediated pictures of clinical allergy by the nonimmunological pathway.
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PMID:Structure and function of IgE myeloma protein VL from an atopic patient. 864 91


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