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)

In this investigation we have evaluated the feasibility of using the polymerase chain reaction (PCR) for hepatitis delta virus (HDV) RNA detection, cloning and sequencing. Total RNA from HDV-infected liver and serum samples was purified and Moloney murine leukaemia virus (M-MLV) reverse transcribed. HDV cDNA was then directly amplified with Taq polymerase using three pairs of specific primers. It was possible to amplify a region of about 1200 bp in three partially overlapping fragments including the whole HDAg-ORF. A DNA fragment of the expected size was repeatedly obtained from an initial sample of less than 0.1 pg of liver RNA and from 10 pl of infected serum. An amplified fragment of 359 bp obtained by PCR from an infected woodchucks' liver was sequenced. The sequence was 91.8% and 98.6% identical to previously published HDV sequences. In addition, amplified and 32P-radiolabelled HDV sequences were shown to hybridize specifically to HDV RNA extracted from HDV-infected liver and serum. In conclusion this technique promises to be of great value in the appraisal of HDV infection, rapid synthesis of HDV probes and analysis of the genetic variability of the virus.
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PMID:Amplification of hepatitis delta virus RNA sequences by polymerase chain reaction: a tool for viral detection and cloning. 231 96

The nucleotide sequence of the internal region of a Drosophila retrotransposon. 412, was determined. The genome of 412 was found to consist of two long open-reading frames (ORFs 1 and 2), an unusually long putative leader region and long terminal repeats (LTRs). As with 17.6, 297 and gypsy, ORFs 1 and 2 slightly overlap each other and are out of phase by +2. ORF2 includes the nucleotide sequences coding for the putative protease, reverse transcriptase and integrase, and is similar in entire organization to the pol gene of Moloney murine leukaemia virus. In spite of the difference in insertion specificity, integrase, an enzyme presumably responsible for insertion, was found to be similar in amino acid sequence to the counterparts of 17.6, 297 and gypsy. There is no ORF in 412 which corresponds to retroviral env or ORF3s of 17.6 and 297. Analysis of 412 transcripts suggested that 412 LTR is composed of U3, R and U5. The gene for a potential primer tRNA for putative reverse transcription of 412 was also surveyed and the 3'-terminal 15 nucleotides of a putative arginine tRNA were found to be exactly complementary to the putative primer-binding site of 412.
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PMID:Nucleotide sequence characterization of a Drosophila retrotransposon, 412. 242 8

The expression of three EBV open reading frames (ORF's), BBRF3, BILF1 and BMRF2 in Epstein-Barr virus (EBV)-transformed B lymphocytes from ataxia-telangiectasia (A-T) homozygotes, was studied. A-T is a human recessive genetic disorder which predisposes homozygotes and heterozygotes to cancer. Computer analysis (Robson-Garnier) was used to study the secondary structure of EBV ORF's. Three ORF's (BBRF3, BILF1 and BMRF2) found by the Kyte and Doolittle computer method to have multiple hydrophobic domains in the putative polypeptides were selected, and the polypeptides were selected, and the respective cloned EBV DNA fragments were used as probes to detect mRNA in the normal and L-6 A-T lines that was not present in the L-15 A-T line. The probe for BILF1 detected two mRNA species (3.7 and 2.0 kb) in the normal lymphoblastoid and A-T L-6 lines, while only the 3.7 kb mRNA was expressed in the A-T L-15 lymphoblasts. The probe for BMRF2 detected two mRNA species (3.7 and 2.1 kb) in the EBV-transformed normal lymphoblasts and in one A-T line (L6). The BMRF2 mRNAs were not detected in the other A-T line (L-15). This study indicated that regulation of the three EBV genes in two EBV-transformed A-T lymphoblastoid lines, differs from that in the EBV-transformed normal lymphoblastoid line. In the A-T line L-6, the three EBV genes were expressed as in EBV-transformed lymphoblastoid cells originating from a normal donor (L-21) and in the P3HR1 Burkitt's lymphoma cell line. The A-T line L-15 differed from L-6 and the other cell lines in that it expressed only one (3.7 kb) RNA species from BILF1 ORF, while ORFs BBRF3 and BMRF2 were not expressed. Since A-T L-15 line contains EBV DNA genomes, and EBV VCA is not present in these cells prior to or after TPA treatment, it is suggested that EBV gene expression is regulated by these A-T lymphoblastoid cells in a manner different from that which operates in other EBV transformed cell lines.
Leukemia 1988 Dec
PMID:Differential expression of Epstein-Barr virus (EBV) genes BBRF3, BILF1, and BMRF2 in EBV-transformed lymphoblastoid lines from ataxia-telangiectasia patients. 284 95

The X region of the human T-cell leukemia virus type I contains the second coding exon of the tax and rex regulatory proteins (open reading frame IV [ORF IV] and ORF III, respectively), as well as coding regions for more recently described proteins, p30II (or the tof protein) and p13II in ORF II and the putative rof protein and p12I in ORF I. Deletions and transcomplementation experiments showed that expression of the envelope, as well as that of the tax and rex proteins, was independent of the proteins encoded in the ORF I/ORF II region. Furthermore, p30II and p12I proteins could not replace the rex protein in a rex-dependent envelope or Gag protein expression system.
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PMID:The open reading frame I (ORF I)/ORF II part of the human T-cell leukemia virus type I X region is dispensable for p40tax, p27rex, or envelope expression. 815 7

We have recently demonstrated the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured bone marrow (BM) stromal dendritic cells from all patients with myeloma studied. To show that these findings were not an artifact of tissue culture, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect KSHV in BM core biopsies. Using ISH to open reading frame-72 (ORF 72), we localized KSHV to BM dendritic cells in 17 of 20 patients with myeloma, 2 patients with plasmacytosis associated with the acquired immunodeficiency syndrome, and 1 case of aplastic anemia. In contrast, BM from normal subjects (n = 4) and patients with lymphoma and leukemia (n = 21) did not contain KSHV. PCR amplification with KSHV primers demonstrated product in fresh BM biopsy samples from 6 of 7 myeloma patients, whereas three normal marrows contained no amplified product. These findings suggest that KSHV, possibly through alterations in the BM microenvironment and production of viral interleukin-6 (vIL-6), may stimulate and maintain abnormal plasma cell proliferation in myeloma and related disorders.
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PMID:Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. 978 98

The soybean genome hosts a family of several hundred, relatively homogeneous copies of a large, copia/Ty1-like retroelement designated SIRE-1. A copy of this element has been recovered from a Glycine max genomic library. DNA sequence analysis of two SIRE-1 subclones revealed that SIRE-1 contains a long, uninterrupted, ORF between the 3' end of the pol ORF and the 3' long terminal repeat (LTR), a region that harbors the env gene in retroviral genomes. Conceptual translation of this second ORF produces a 70-kDa protein. Computer analyses of the amino acid sequence predicted patterns of transmembrane domains, alpha-helices, and coiled coils strikingly similar to those found in mammalian retroviral envelope proteins. In addition, a 65-residue, proline-rich domain is characterized by a strong amino acid compositional bias virtually identical to that of the 60-amino acid, proline-rich neutralization domain of the feline leukemia virus surface protein. The assignment of SIRE-1 to the copia/Ty1 family was confirmed by comparison of the conceptual translation of its reverse transcriptase-like domain with those of other retroelements. This finding suggests the presence of a proretrovirus in a plant genome and is the strongest evidence to date for the existence of a retrovirus-like genome closely related to copia/Ty1 retrotransposons.
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PMID:SIRE-1, a copia/Ty1-like retroelement from soybean, encodes a retroviral envelope-like protein. 961 10

Human CEM-7A cells established by gradual deprivation of leucovorin from the growth medium, display 100-fold overexpression of methotrexate transport activity. We found that this was associated with 10-fold reduced folate carrier gene amplification and 50-fold overexpression of both the principal 3 kb reduced folate carrier transcript and, surprisingly, a novel truncated 2 kb reduced folate carrier mRNA poorly expressed in parental CEM cells. The molecular basis for the generation of this truncated reduced folate carrier transcript and its potential functional role in folate accumulation were studied. Reduced folate carrier genomic and cDNA sequencing revealed that the truncated transcript had an internal deletion of 987 nucleotides which was a result of an alternative splicing utilizing a cryptic acceptor splice site within exon 6. This deletion consisted of the 3'-most 480 nucleotides of the reduced folate carrier ORF and the following 507 nucleotides of the 3'-UTR. These resulted in a truncated reduced folate carrier protein, which lacks the C-terminal 160 amino acids, but instead contains 58 new C-terminal amino acids obtained from reading through the 3'-UTR. Consequently, a truncated reduced folate carrier protein is generated that lacks the 12th transmembrane domain and contains a new and much shorter C-terminus predicted to reside at the extracellular face. Western analysis with plasma-membrane fraction from CEM-7A cells revealed marked overexpression of both a broadly migrating approximately 65-90 kDa native reduced folate carrier and a approximately 40-45 kDa truncated reduced folate carrier, the core molecular masses of which were confirmed by in vitro translation. However, unlike the native reduced folate carrier, the truncated reduced folate carrier protein failed to bind the affinity labels NHS-[3H]MTX and NHS-[3H]folic acid. Stable transfection of the truncated reduced folate carrier cDNA into mouse L1210 leukemia cells: increased folate accumulation, decreased their leucovorin and folic acid growth requirements, and increased their sensitivity to methotrexate. This constitutes the first documentation of an expressed alternatively spliced truncated reduced folate carrier that, when coexpressed along with the native carrier, augments folate accumulation and consequently decreases the cellular folate growth requirement. The possible mechanisms by which the truncated reduced folate carrier may increase folate accumulation and/or metabolism in cells coexpressing the truncated and native reduced folate carrier are discussed.
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PMID:Characterization of a human alternatively spliced truncated reduced folate carrier increasing folate accumulation in parental leukemia cells. 1065 5

We have identified a gene at 11q23, telomeric to MLL, that encodes a guanine nucleotide exchange factor (GEF). This gene is transcribed into a 9.5-kb mRNA containing a 4.6-kb ORF. By Northern analysis, it was found to be expressed in all human tissues examined including peripheral blood leukocytes, spleen, prostate, testis, ovary, small intestine, colon, and minimally in thymus. Analysis of the predicted protein sequence indicates that it has strong homology to several members of the family of Rho GEFs that includes such oncogenes as Dbl, Vav, Tiam, and Bcr. A patient with primary acute myeloid leukemia (AML) and a karyotype of 51,XY,+8,+19,+3mar was found to have the 5' end of MLL at exon 6 fused in-frame with the 3' end of almost the entire ORF of this gene, which we named LARG for leukemia-associated Rho GEF. Transcriptional orientation of both genes at 11q23 is from centromere to telomere, consistent with other data that suggest the MLL-LARG fusion resulted from an interstitial deletion rather than a balanced translocation. LARG does not appear to have any homology with other MLL partner genes reported thus far. Thus, LARG represents an additional member of the GEF family and a novel MLL fusion partner in acute myeloid leukemia.
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PMID:Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia. 1068 37

Dystroglycan is a laminin binding protein, which provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix. It is also involved in the organization of basement membranes. So far the genomic organization of the dystroglycan gene DAG1 has not been completely investigated. Here we report the cloning and sequencing of 162 kb of dog genomic DNA containing the complete approximately 71-kb canine DAG1 gene, which consists of three exons, with the translation start codon located in exon 2. Its 2679-nucleotide ORF encodes a polypeptide of 892 amino acids, which is highly similar to human, rabbit, and bovine orthologs. To further characterize the dog DAG1 gene we determined the transcription start site and several naturally occurring polymorphisms, which partially result in amino acid substitutions of the dystroglycan protein. The dog DAG1 gene was assigned to chromosome 20q15.1-q15.2 by FISH analysis. The analysis of the entire reported sequence revealed that the genes for aminomethyltransferase (AMT), bassoon (BSN), TCTA (T-cell leukemia translocation-associated) gene, and an as yet uncharacterized protein are located very close to the DAG1 gene. Therefore, this study defines a novel syntenic region among dog chromosome 20q15, human chromosome 3p21, and murine chromosome 9F.
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PMID:Genomic organization of the dog dystroglycan gene DAG1 locus on chromosome 20q15.1-q15.2. 1072 May 70

Human T cell leukemia/lymphotropic virus types 1 and 2 are two immunologically and phylogenetically related retroviruses that differ in their pathogenicity in vivo. The overall genetic structure of HTLV-1 and -2 is similar. Each contains a unique region at the 3' end of the genome, designated the pX region. p12(I) is a membrane-associated protein encoded by the open reading frame I (ORF I) region of HTLV-1, which lies within the pX region. A corresponding protein, p10(I) is encoded by the ORF I region of HTLV-2 and an additional protein, p11(V), is encoded by ORF V, which overlaps the HTLV-2 ORF I region. As with HTLV-1, the small proteins encoded by the pX region of HTLV-2 appear to be dispensable for viral replication and cellular transformation in vitro. However, the small open reading frames of both viruses are important for viral replication in vivo, which suggests they may play an important role during the viral life cycle. This study was undertaken to investigate and compare the cellular targets of the p10(I), p11(V), and p12(I) putative proteins.
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PMID:The MHC class I heavy chain is a common target of the small proteins encoded by the 3' end of HTLV type 1 and HTLV type 2. 1108 Aug 26


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