Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NH2-terminal amino acid sequences (initial 23 residues) of Friend murine leukemia virus gp71 and gp69 were determined and found to be different but highly related. Friend murine leukemia virus gp71 differed from Rauscher murine leukemia virus gp70 in only one position. Friend murine leukemia virus gp69 showed approximately 41% homology to these glycoproteins but lacked the glycosylation site (sequon) occurring at position 12 in Rauscher murine leukemia virus gp70.
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PMID:Glycoproteins of friend murine leukemia virus: separation and NH2-terminal amino acid sequences of gp69 and gp71. 708 61

Several 1-N-substituted derivative [haloacetyl-, glycyl-, (dimethyl)amino-acetyl-, azidoacetyl-, trifluoroacetyl-, and trifluoromethylsulfonyl-] of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-beta-D-glucopyranosylamine (1) were synthesized as potential metabolic inhibitors of cellular-membrane glycoconjugates. Several fully acetylated derivatives were found to inhibit growth of mouse mammary adenocarcinoma TA3, leukemia L1210, or leukemia P-288 cells at 1-0.01 mM concentration in vitro. Some of these derivatives were less active after O-deacetylation. Analogs of 1 in which NH2-1 was replaced by OH- or OAc-1 were also active on the same cell systems. The growth-inhibitory activity was correlated with inhibition of the incorporation of 2-amino-deoxy-D-glucose and L-leucine into a macromolecular fraction.
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PMID:Synthesis and biological activity of some 1-N-substituted 2-acetamido-2-deoxy-beta-D-glycopyranosylamine derivatives and related analogs. 736 76

The principal surface glycoprotein which specifically binds immunoglobulin E was isolated from rat basophilic leukemia cells in sufficient amounts for compositional and end group analyses. The protein has about 30% carbohydrate and a relatively low content of hydrophobic amino acid residues. No NH2-terminal residue was found by standard methods. The data suggest a Mr approximately equal to 50,000. The latter value is calculated on the basis of 1 molecule of receptor binding 1 molecule of immunoglobulin E. New data confirmed this valence. We propose a provisional model in which the principal component which binds immunoglobulin E is a monomer which, in cells and in nondenaturing solvents, is associated in a 1:1 ratio with the polypeptide of Mr approximately equal to 30,000 recently defined by studies employing cross-linking reagents.
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PMID:Composition and subunit structure of the cell receptor for immunoglobulin E. 741 Apr 11

In murine leukemia virus-induced myeloid leukemias, insertional mutagenesis of the c-myb locus has been shown to occur frequently. Proto-oncogene activation is achieved in most leukemias by integration of murine leukemia virus upstream of exons 3 or 4 or by integration into exon 9 with consequent truncation of the protein. The present study investigates the effect of ectopic expression of full-length c-myb or c-myb containing amino- or carboxyl-terminal truncations (minus 47 and 248 amino acids, respectively) on granulocyte differentiation in vitro. Recombinant myb retroviruses were used to infect an interleukin 3-dependent progenitor cell line, 32Dcl3, which undergoes terminal differentiation to mature neutrophilic granulocytes in the presence of granulocyte colony-stimulating factor. Overexpression of c-myb did not abrogate the interleukin 3 dependency of the parental cell line. However, cells expressing all forms of c-myb were blocked at an intermediate stage of granulocyte differentiation and continued to proliferate in the presence of granulocyte colony-stimulating factor. After 14 days in medium with granulocyte colony-stimulating factor, myb-expressing cultures predominantly consisted of promyelocytes with some myelocytes and almost undetectable numbers of neutrophilic granulocytes. This suggested that early stages of granulocyte differentiation were not inhibited, a finding that was further supported by the induction of myeloperoxidase, a biochemical marker of promyelocytes. Interestingly, the expression of lactoferrin, known to be a marker of late stages of granulocyte differentiation, was completely inhibited in the cells infected with myb viruses. It was concluded that c-myb expression blocked granulocyte differentiation to the terminal mitotic stages and that deletion of the NH2-terminal 47 amino acids and/or the COOH-terminal 248 amino acids of c-myb neither enhanced nor diminished this effect.
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PMID:Only late, nonmitotic stages of granulocyte differentiation in 32Dcl3 cells are blocked by ectopic expression of murine c-myb and its truncated forms. 753 40

The HRX gene has recently been shown to be involved in most of the chromosomal abnormalities of band 11q23 frequently present in human hematological malignancies. Rearrangements are strikingly diverse, but most affect a restricted area of the HRX gene and lead to gene fusion between HRX and a gene located on the partner chromosome. Another kind of HRX alteration seen in human acute leukemia is a partial duplication of the NH2 part of the HRX locus. We have characterized two cases of partial HRX duplication in acute leukemias bearing trisomy 11 as the sole chromosomal abnormality. In one patient analyzed at the genomic level, an Alu repeat was involved within exon 6 but not within intron 1. Splicing of exon 6 to exon 2 was observed in this patient while splicing of exon 8 to exon 2 was observed in the other. Our data indicated that HRX duplication is highly similar to the translocation affecting the HRX locus both in the restricted diversity of the fusion points and the involvement of Alu repeats within the breakpoint cluster region (exon 5 to 10).
Leukemia 1995 Sep
PMID:Partial duplication of HRX in acute leukemia with trisomy 11. 765 17

The monoclonal antibody C215 (IgG2a) was obtained by the immunization of BALB/c mice with the human colon adenocarcinoma cell line COLO 205 and used in the targeting of colorectal carcinomas. The partial characterization and purification of the C215 target molecule from solubilized COLO 205 membranes indicated that it is an integral membrane glycoprotein of the non-mucin type. The denatured antigen appeared as a major 40-kDa form in Western blots after SDS-polyacrylamide gel electrophoresis and migrated as a monomeric 36-kDa species after the reductive cleavage of intramolecular disulfide bridges. Using a five-step procedure, the antigen was purified 4,300-fold from COLO 205 tumors raised in nude mice to a homogeneity of 95% when assessed by capillary electrophoresis. Removal of N-linked carbohydrate by peptide:N-glycosidase treatment did not affect the visualization of the purified antigen in immunoblots but resulted in a faster migration in the SDS gels. The amino acid sequence was partially determined. Seventeen contiguous NH2-terminal amino acids were identified and coincided exactly with residues 82-98 of the GA733-2 protein cloned by Szala et al. (Szala, S., Froehlich, M., Scollon, M., Kasai, Y., Steplewske, Z., Koprowski, H., and Linnenback, A. J. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3542-3546). Therefore, the predicted amino acid sequence of this protein was used to prepare overlapping synthetic peptides that cover the entire extracellular domain in order to identify the C215 epitope. A likely epitope, close to the NH2 terminus and corresponding to the first distinct hydrophilic stretch after the putative signal sequence, was identified in a peptide enzyme-linked immunosorbent assay. Moreover, GA733-2 cDNA was used for the cloning of the C215 protein from COLO 205 cells and the subsequent transfection to K36.16 mouse T cell leukemia cells. The transfected cells were C215 reactive in fluorescence-activated cell sorter analysis, and a 42 kDa band was visualized in Western blots under both non-reducing and reducing conditions. Our findings indicate a close relationship between the C215 antigen and other members of the GA-733 family, some of which are currently being used as targets in clinical trials with monoclonal antibodies. The mammalian expression system described here will enable further studies into the biological role of this protein and the construction of animal models in order to develop optimal therapeutic strategies.
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PMID:Isolation, partial characterization, and molecular cloning of a human colon adenocarcinoma cell-surface glycoprotein recognized by the C215 mouse monoclonal antibody. 769 97

In addition to the known 94-kd gelatinase (matrix metalloproteinase 9, MMP-9), HL-60 leukemia cells release a hither-to undescribed 45-kd metalloproteinase into the culture medium. This enzyme cleaves the synthetic substrate Pro-Gln-Gly-Ile-Ala-Gly-Gln-Arg, which represents the cleavage site for collagenases in collagen type I not between isoleucine and alanine--the typical cleavage site for collagenases--but between alanine and glycine. The enzymatic activity was purified through a combination of zinc-chelate-Sepharose column chromatography, precipitation with Fractogel TSK-AF Red and gelatin-Sepharose, and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Microsequence analysis of the NH2-terminus of the purified 45-kd proteinase revealed the sequence Asp-Ile-Ser-Lys-Tyr-Thr-Thr-Thr-, which could not be found in other proteins when searched in several protein data bases. Incubation of the enzyme immobilized on nitrocellulose membranes with polyclonal antibodies to collagenase and stromelysin or gelatinases revealed no cross-reactivity. The proteolytic activity was not increased by treatment with trypsin, 8M urea, acid, or organomercurials. The proteinase, which was inhibited by chemical inhibitors of metalloproteinases, such as phenanthrolene or EDTA, is able to degrade several matrix constituents, such as collagen type IV, fibronectin, gelatin, and proteoglycans. In contrast to all known MMPs, the proteolytic activity of the 45-kd enzyme was not abolished upon incubation with recombinant tissue inhibitors of matrix metalloproteinases (TIMP) 1 or 2. Thus, the novel enzyme may influence extracellular matrix (ECM) turnover in vivo because its activity is not influenced by specific inhibitors of MMPs.
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PMID:Leukemic cells (HL-60) produce a novel extracellular matrix-degrading proteinase that is not inhibited by tissue inhibitors of matrix metalloproteinases (TIMPs). 782 72

Three homologous alicyclic mixed amine cis-(NH3)(R-NH2)Cl2Pt(II) complexes, in which R = C3H5, C6H11, and C8H15 (complexes abbreviated C3, C6, and C8, respectively), were evaluated with reference compounds cisplatin and tetraplatin for antitumor activities and biochemical pharmacology in wild-type (murine leukemia L1210/0 and human ovarian A2780) and corresponding variant cell lines resistant to cisplatin (L1210/DDP and 2780CP) and tetraplatin (L1210/DACH and 2780TP). Cytotoxicities, measured by either a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or a clonogenic assay, were maximal for the C6 complex, which was up to 12-, 40-, and 6-fold more potent than C3 against wild-type, cisplatin-resistant, and tetraplatin-resistant models, respectively, and up to 2-fold more potent than C8 against these cell lines. In general, cross-resistance to mixed amine analogues was partial in cisplatin- and tetraplatin-resistant cells and decreased (in L1210/DDP and 2780CP) or increased (in L1210/DACH and 2780TP) with increase in the alicyclic ring size. The increase in ring size resulted in a corresponding increase in partition coefficient, which correlated directly with intracellular accumulations of mixed amine analogues in all cell lines. However, the intracellular DNA-platinum adducts, and not cellular platinum content, was the pharmacological entity that corresponded closely to potencies of the molecules. DNA adduct formation was disproportionate to the level of cellular drug accumulation. For instance, complex C8, which accumulated to the greatest extent in any given cell line, produced adduct levels that were similar to or lower than those produced by C6. A partial explanation for this observation was the demonstrated reduced rate of binding of C8 to DNA. This study has highlighted the significance of alicyclic ring size in modulating the potency, cross-resistance profile, and biochemical pharmacology of mixed amine platinum(II) complexes in sensitive and cisplatin- or tetraplatin-resistant tumor cells.
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PMID:Biochemical pharmacology of homologous alicyclic mixed amine platinum(II) complexes in sensitive and resistant tumor cell lines. 801 68

A series of C-6-substituted methyl mitomycins was synthesized and evaluated for anticellular and antitumor activities. These novel compounds were prepared by Michael addition of various alcohols or thiols to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosanes followed by treatment with NH3 or MeOH/K2CO3. Most compounds were potent against HeLa S3, and some of them showed superior activity to that of mitomycin C (MMC) against P388 leukemia and sarcoma 180 in mice. In addition, some compounds exhibited remarkable activity against MMC-resistant P388 in mice. FAB-MS spectra of these mitomycin derivatives showed the elimination of the C-6-methyl substituents from the mitomycin skeletons to form quinonemethides. Interestingly, treatment of 6-demethyl-6-[[(2-pyrimidinyl)thio]methyl ]mitomycin C (12v) with diethylamine afforded 6-demethyl-6-[(diethylamino)methyl]mitomycin C (31) in good yield. These results suggested that the C-6-substituted methyl mitomycins would have different biological character from that of MMC.
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PMID:Synthesis and antitumor activity of novel mitomycin derivatives containing functional groups at the C-6-methyl position. 802 18

We have biochemically purified a 27-kDa serine protease (designated RNK-Tryp-2) from the granules of the rat large granular lymphocyte leukemia cell line (RNK-16) which has tryptase activity. Utilizing molecular sieve chromatography and reverse-phase HPLC, we purified RNK-Tryp-2 to homogeneity and sequenced 33 NH2-terminal amino acids. Oligonucleotide primers were used in the PCR to generate a 528-bp cDNA clone encoding a novel serine protease from RNK-16 mRNA. This cDNA clone was used to isolate an 884-bp RNK-Tryp-2 cDNA from an RNK-16 lambda-gt11 library. The open reading frame predicts a mature protein of 233 amino acids which does not have potential sites for N-linked glycosylation. The cDNA encodes a leader peptide of at least 25 amino acids. The characteristic Ile-Ile-Gly-Gly amino acids of the N-terminus, and the His, Asp, and Ser amino acids that form the catalytic triad of serine proteases, are conserved. The amino acid sequence has less than 45% identity with any other member of the serine protease family, indicating that RNK-Tryp-2 is distinct protease. Southern blot analysis suggests the existence of one or more related genes. A single 1.3-kb mRNA transcript was detected by Northern blot analysis of total cellular RNA from the in vivo passaged RNK-16, rat splenocytes, lung and liver nonparenchymal cells, as well as in highly purified rat LGL and T cells. RNK-Tryp-2 is a novel serine protease that is expressed in the granules of large granular lymphocytes.
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PMID:Purification and cloning of a novel serine protease, RNK-Tryp-2, from the granules of a rat NK cell leukemia. 813 42


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