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)

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

The author engaged himself in the studies of ABO blood group system for the last three decades, and reviewed the progresses in this period, which were classified into following 5 items. 1. H-, A- and B-active oligosaccharides were isolated from the globoside fractions from human erythrocytes by ozonolysis. One of the H-active oligosaccharide with short carbohydrate chain is a pentasaccharide: Fuc(alpha 1-->2)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc, and the other with long carbohydrate chain is a heptasaccharide: Fuc(alpha 1-->2)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc. Hexa- or octasaccharides with blood group A- or B-activity have an additional alpha-N-acetylgalactosaminyl residue or alpha-galactosyl residue, which joints with alpha 1-->3 linkage to subterminal beta-galactose of the both of H-active oligosaccharides, respectively. 2. A blood group A-gene specified alpha-N-acetyl-galactosaminyltransferase (A-enzyme) catalyzes the transfer of N-acetylgalactosamine from the UDP-sugar to the subterminal beta-galactosyl residue of blood group H-active carbohydrate chain, and a blood group B-gene specified alpha-galactosyltransferase (B-enzyme) catalyzes the transfer of galactose from the UDP-sugar to the subterminal beta-galactosyl residue of blood group H-active carbohydrate chain, respectively. Either the A- or B-enzyme can not transfer the substrate sugar to the carbohydrate chain lacking alpha-fucosyl residue of H-determinant, and it is the reason why the synthesis of blood group A- or B-antigenic structure in inhibited in the tissues of Bombay phenotype and in the secretory glands of the nonsecretor. 3. Specific antibody either to the A- or B-enzyme can be introduced in the serum of the rabbit which was immunized with the A- or B-enzyme preparation, respectively. And immunological cross reaction is also present between the A- and B-enzyme, but the immunologically cross reactive material can not be found in the blood group O individual. The absence of immunologically cross reactive material in the blood group O individual is supported by a fact that the cross reactive antibody similar to the antibody in rabbit serum was present in the serum of the chronic myeloid leukemia patient, who was belonged to blood group B and treated with blood group incompatible bone marrow transplantation from blood group O donor, because it is acceptable to speculate that the grafted lymphocytes react to the B-enzyme in the recipient and produce the anti-enzyme antibody. 4. The immunological profiles described above are compatible with the cDNA structures of human blood group ABO alleles presented by Yamamoto F. et al. Their gene model is that the cDNAs of blood group ABO alleles are highly homologous, but the cDNA of common O allele is non-functional due to a single nucleotide deletion close to the 5'end of the coding sequence, which causes a frame shift of the codon, and results in truncated peptide. 5. Transcription of the human blood group ABO gene can be enhanced by a CBF/NF-Y which binds the minisatellite on the 5'-upstream sequence of the gene.
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PMID:[Past and present studies on ABO blood group system]. 1007 71

Nilotinib is a novel BCR-ABL inhibitor with significantly improved potency and selectivity over imatinib. In Phase I and Phase II clinical studies of nilotinib in patients with a variety of leukemias, infrequent instances of reversible, benign elevation of bilirubin were observed. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinemia during treatment with a number of drugs. Pharmacogenetic analysis of that TA-repeat polymorphism found an association between the (TA)7/(TA)7 genotype and risk of hyperbilirubinemia in Phase I patients with imatinib-resistant/intolerant chronic myeloid leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL); this result was replicated in two separate analyses of the chronic phase (CP) and accelerated phase (AP) CML arms of a Phase II study. As nilotinib is not known to be glucuronidated by UGT1A1, the combined impact of inhibition of UGT1A1 activity by nilotinib and genetic polymorphism is the most likely cause of the increased rate of hyperbilirubinemia.
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PMID:UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. 1761 64