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)

To isolate murine purine nucleoside phosphorylase-encoding cDNA sequences (PNP), a murine BALB/c liver cDNA library in lambda gt10 was screened for recombinants hybridizing to a human PNP cDNA probe. Two of three clones recovered included inserts large enough to contain the full-length coding sequence. Sequence analysis of the largest clone revealed an 867-nucleotide open reading frame encoding 289 amino acids with 84% residue identity to that encoded by human PNP and 351 bp of 3'-untranslated region. The 5' end of the murine PNP message was specifically amplified by PCR using the RACE (rapid amplification of cDNA ends) protocol, revealing a 5'-untranslated region of 78 bp. Northern hybridization using the murine PNP cDNA sequence as a probe identified a message of approx. 1.6 kb in mouse NIH3T3 cells which was slightly smaller than the human message observed in HeLa cells. The cloned murine PNP cDNA coding sequence was inserted into a mammalian expression vector under transcriptional regulation of the Moloney murine leukemia virus long terminal repeat. Transfection of this plasmid into human 293 cells resulted in the expression of PNP activity which co-focused with murine PNP activity extracted from NIH3T3 cells, verifying that the isolated murine PNP cDNA clone encoded catalytically active PNP protein.
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PMID:Isolation and expression of a murine purine nucleoside phosphorylase-encoding cDNA and sequence similarity with the human message. 137 46

A cDNA encoding a novel rat mast-cell proteinase (MCP) named rMCP-3 was successfully cloned and sequenced from the peritoneal cells of Lewis rats infected with the intestinal nematode Nippostrongylus brasiliensis by using the combination of reverse transcription-PCR and rapid-amplification-of-cDNA-ends ('RACE') methods. The cDNA was 979 bp long and included a 741 bp open reading frame. When the deduced amino acid sequence was compared with those of other known mast-cell proteinases, rMCP-3 was considered to be translated as a preproenzyme with a 19-amino-acid signal peptide, a two-amino-acid activation peptide and a 226-amino-acid mature enzyme. The amino acid identity in the mature enzyme was 52.9% and 55.1% with rMCP-1 and rMCP-2 respectively. The rMCP-3 mRNA was not detected in the peritoneal cells of mast-cell-deficient Ws/Ws rats, though it was strongly detected in those of littermate +/+ and Lewis rats, indicating the mast-cell origin of rMCP-3 In addition to being present in peritoneal mast cells, the rMCP-3 mRNA was strongly detected in the skin, tongue, and RBL2H3 rat basophilic leukaemia cells and weakly in the jejunum of N. brasiliensis-infected rats by RNA blot analysis using a rMCP-3 gene-specific probe. By reverse transcription-PCR, the rMCP-3 mRNA was also detected in the lung. While the expression of rMCP-1 and rMCP-2 are clearly restricted in connective-tissue mast cells and mucosal mast cells respectively, rMCP-3 was widely expressed in both types of mast cells with a predominance in connective-tissue mast cells.
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PMID:Cloning of the cDNA encoding a novel rat mast-cell proteinase, rMCP-3, and its expression in comparison with other rat mast-cell proteinases. 748 12

Positional cloning of the putative gene responsible for transient abnormal myelopoiesis (TAM) and that for multiple cartilaginous exostoses (MEX) is described. TAM is a leukemoid reaction occurring frequently in Down syndrome (DS) newborn infants and they often develop true leukemia several years later. The previous findings of "disomic homozygosity in trisomic cells" and tentative mapping of the TAM gene to 21q11.1, and an encounter of a unique DS-associated TAM patient with inv(21) (q11.1q22.13) let us start positional cloning of the TAM gene. One type of MEX is an autosomal dominant disorder and patients with MEX sometimes develop chondrosarcoma. The MEX gene has been mapped to 8q24. We encountered a sporadic case of MEX with de novo t(8q; 13q). Thus, we hypothesized that in both patients, the TAM and the MEX genes are disrupted by the structural chromosome abnormalities. For TAM, we first mapped the proximal breakpoint of inv(21) between 2 STSs using 7 cosmid clones as FISH probes that were isolated on the basis of STS markers at the 21q11.1 region, isolated their corresponding YACs, and then analyzed them. However, since YACs corresponding to 2 other STSs between the two markers could not be isolated, we carried out a chromosome walking to construct a cosmid contig between the 2 STSs. Southern analysis with a cosmid clone within the contig detected EcoRI-/HindIII extra bands on the patient's DNA. The cDNA screening and exon trapping to isolate a gene from the region are underway. Similarly, in the MEX patient we mapped the 8q breakpoint between 2 cosmid markers, then isolated YACs and cosmid subclones. By exon trapping after detection of a cosmid covering the breakpoint, an exon-like sequence was isolated. The 3'-RACE/5'-RACE revealed a novel transcript from this cosmid. Whether the transcript is the MEX gene remains to be determined.
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PMID:[Positional cloning of the putative gene responsible for transient abnormal myelopoiesis and that for multiple cartilaginous exostoses]. 869 34

Based on previously published observations regarding the protective effects of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) against gamma radiation, alkylating agents and ultraviolet radiation, we hypothesized that the protection against such DNA damaging treatments can be the result of a 'stress'-like response induced by these cytokines and mediated by early response cellular gene(s). By applying the mRNA differential display to RNA obtained from A549 lung carcinoma cell line that was incubated with 50 ng/ml IL-1 for 0, 1, 2, and 6 h, we identified several cDNA fragments that correspond to genes regulated by IL-1. The full length cDNA for one fragment was obtained using 5'RACE, cloned, sequenced, and found to be homologous to human A1, a Bcl-2-related gene. In this study, we report that the expression of human A1 is either absent or present at low levels in leukemic cells, while it is expressed in human bone marrow cells and abundant in peripheral blood progenitors. It is induced by IL-1 and TNF alpha in A549 lung carcinoma, bone marrow, and certain leukemic cells. A1 is also induced in leukemic cells during granulocytic or macrophage but not erythroid differentiation. In conclusion, this is the first demonstration that A1 is inducible by cytokines in human bone marrow and certain tumor cells as well as myeloid differentiation in leukemic cells.
Leukemia 1997 Jul
PMID:Human A1, a Bcl-2-related gene, is induced in leukemic cells by cytokines as well as differentiating factors. 920 81

Involvement of the ETV6 gene, located at 12p13, has been investigated in 20 patients with an abnormality of the short arm of chromosome 12 (abn 12p) detected cytogenetically. Patients in the study had c/pre-B acute lymphoblastic leukemia (ALL) (nine children and three adults), T-ALL (three adults), acute myeloid leukemia (AML) (two adults), biphenotypic acute leukemia (Bip-L) (one adult), myelodysplasia (MDS) (one adult) and chronic myelomonocytic leukemia (CMML) (one child). Abnormalities of 12p comprised deleted (del)(12p) alone (seven cases), add(12p) alone (seven cases), del(12p) and add(12p) (one case) and balanced translocations of 12p to 1p13, 1q31, 10q11, 14q11 and 15q15 (one case of each). A novel, exon-specific RT-PCR assay identified breakpoints in ETV6 in nine of 19 cases, and showed breakpoints in intron 5 (seven cases of children with c-ALL), in intron 4 (in one adult with Bip-L) and in intron 2 (in one adult with AML). RT-PCR for the ETV6/AMLI fusion (tested in 19 cases) was positive using standard primers in five cases (four of which had shown rearrangements in intron 5) and occurred as a variant fusion in a sixth case (also positive for a rearrangement in intron 5) using 3' RACE PCR. Southern blotting confirmed rearrangements in intron 5 in the five cases available for analysis and revealed a rearrangement in intron 5 in one of 10 cases with no evidence of intron 5 involvement by RT-PCR. Rearrangements in intron 5 of ETV6 were found in eight of nine cases of children with c-ALL of which six carried the ETV6/AMLI fusion. Heterozygosity within intron 5 (revealed by the genomic probe B1) was found in seven of 11 cases tested. Deletion of one allele was indicated in three cases with del(12p) and one case with add(12p). This study, using a combination of ETV6 exon-specific RT-PCR, RT-PCR for ETV6/AMLI and Southern blotting has shown that rearrangement and/or deletion of ETV6 may occur in up to 70% of patients with abn 12p. Furthermore, 90% of children in this study with an abn 12p and c-ALL, carried a rearrangement of ETV6 in intron 5.
Leukemia 1998 Jul
PMID:Abnormalities of the ETV6 gene occur in the majority of patients with aberrations of the short arm of chromosome 12: a combined PCR and Southern blotting analysis. 966 96

The cell surface receptor for gibbon ape leukemia virus (Glvr-1) belongs to the type III sodium-dependent phosphate transporter/retrovirus receptor gene family. Several observations have suggested an important role for Glvr-1 in regulated Pi handling in bone forming cells and prompted us to investigate further the molecular mechanisms regulating Glvr-1 gene expression. In addition, the regulation of Glvr-1 gene expression also has potential applications to gene therapy, since retroviral vectors carrying gibbon ape leukemia virus envelope proteins are used for gene delivery into different cell types. The aim of this study was thus to clone the human Glvr-1 gene in order to describe its structure and its promoter region. Our results indicate that the Glvr-1 gene consists of 11 exons and 10 introns spread over 18kb of genomic DNA. The translation initiation site is located within exon II and the translation stop codon within exon XI. Rapid amplification of cDNA ends (5'-RACE) suggests that, in human SaOS-2 osteoblast-like cells, transcription of Glvr-1 is initiated at multiple sites, mostly located between bp 32 and 50 of the published cDNA sequence, which was initially obtained from HL-60 cells. The 5'-flanking region of the gene is characterized by a very high GC content. Reporter gene assays demonstrate the presence of a functional promoter upstream of exon I and indicate that a GC-rich region, containing two potential SP1 binding sites, is required for high promoter activity in transiently transfected SaOS-2 cells. The description of the human Glvr-1 gene structure, as well as the analysis of some structural and functional characteristics of its promoter region, provide a basis for more detailed investigation of the molecular mechanisms controlling expression of the Glvr-1 gene in bone forming cells and in other cell types.
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PMID:Characterization of the human Glvr-1 phosphate transporter/retrovirus receptor gene and promoter region. 988 6

We have recently isolated two cDNAs encoding two forms of transmembrane and cytosolic protein tyrosine phosphatase epsilon (PTPepsilon). In this study, the 5' end of the rat PTPepsilon gene was isolated and characterized. Transmembrane PTPepsilon (PTPepsilonM) and cytosolic PTPepsilon (PTPepsilonC) were encoded by a single gene. 5' RACE analysis and RNase protection assay showed that the mRNA of each PTPepsilon isoform was transcribed from different promoters. The putative promoter regions of two alternative first exons lacked a TATA box, but contained potential recognition sites for several transcription factors. Reverse transcription PCR analysis revealed that PTPepsilonC mRNA was up-regulated during interleukin 6-induced differentiation of murine leukemia M1 cells, whereas PTPepsilonM mRNA was down-regulated. With the use of luciferase as a reporter gene, the promoter activities of the 5'-flanking regions were examined during phorbol myristate acetate-induced differentiation of HL-60 cells. In the differentiated HL-60 cells, the activity of the PTPepsilonC promoter, but not that of PTPepsilonM, was dramatically elevated. Furthermore, we found that PTPepsilonC mRNA is highly expressed in mouse peritoneal macrophages and enhanced during activation by lipopolysaccharide. These results suggest that the different promoters control expression of PTPepsilon isoforms during the differentiation and/or activation of macrophages.
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PMID:Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase epsilon expression during macrophage differentiation. 991 74

A novel cDNA encoding a secreted form of osteoclast differentiation factor/tumor necrosis factor-related activation-induced cytokine (sODF/TRANCE, GenBank Accession No. AB037599) was sequenced from 5' RACE cDNA clones of squamous cell carcinoma cell lines, SCC-4 and T3M-1 Cl.2, of which parental malignant tissues had caused severe humoral hypercalcemia. The sODF/TRANCE cDNA was composed of unknown 5' end sequence followed by the 100% identical sequence of the ODF/TRANCE extracellular domain-coding region. The longest open reading frame (ORF) of the novel cDNA completely matched the 3' end of the ORF of the ODF/TRANCE cDNA encoding C-terminal amino acid residues (74-318) in the extracellular region. The corresponding protein that reacted with the antibody specific for the extracellular domain of ODF/TRANCE was detected in the culture media conditioned by the cancer cells. Furthermore, human promyeloblastic leukemia cells, HL60, differentiated into osteoclast-like cells (OCLs) when cultured in the media conditioned by SCC-4 and T3M-1 Cl. 2 cells. The differentiation of HL60 cells into OCLs was inhibited by the anti-ODF/TRANCE antibody. These results strongly suggest that sODF/TRANCE plays an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
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PMID:Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation. 1070 88

In fucosyltransferase genes, mRNA expression is regulated in a cell-type-specific manner. The expression level of human fucosyltransferase 4 (FUT4) mRNA is high in both colon adenocarcinoma and myeloid cell lines. We will demonstrate here cell-specific expression and transcriptional regulation of the FUT4 gene. FUT4 has two different transcription initiation sites that respectively produce long- and short-form mRNAs. To determine the major FUT4 transcript in colon adenocarcinoma and myeloid cell lines, we analyzed the transcriptional starting sites of the FUT4 gene in myeloid and colon adenocarcinoma cell lines, using 5'-RACE, RT-PCR, and luciferase analysis. The results suggested that the expression level of short-form mRNA is higher than the long-form transcript in the colon adenocarcinoma cell lines and that the expression level of long-form mRNA is higher than the short-form transcript in the myeloid cell lines. Using a luciferase assay, we identified a functional DNA portion within FUT4 genomic DNA that confers a colon adenocarcinoma cell line-specific enhancer, located in nucleotide number (nt) -256 to -44, and a myeloid cell line-specific enhancer, located in nt -686 to -582. The present results suggest that these elements play a critical role in the colon adenocarcinoma and leukemia cell-specific transcriptional regulation of the FUT4 gene.
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PMID:Expression and transcriptional regulation of the human alpha1, 3-fucosyltransferase 4 (FUT4) gene in myeloid and colon adenocarcinoma cell lines. 1087 13

We report the characterization of a rare chromosomal translocation, a t(2;11)(q31;p15), which occurred in a patient with de novo acute myeloid leukemia (AML-M4). By 3'-RACE and RT-PCR analyses, two kinds of NUP98-HOXD13 fusion transcript were detected. In addition, we identified a novel fusion transcript, NUP98-FN1, in the same patient. Ectopic expression of the wild-type HOXD13 gene was also observed in the patient, suggesting that HOXD13 contributes to the development of this type of leukemia. The NUP98-HOXD13 fusion transcript was predicted to encode a 552 or 569-amino acid protein containing the Phe-Gly (FG) repeat region of NUP98 and the homeodomain of HOXD13. The NUP98-FN1 fusion transcript was predicted to encode a 482 or 499-amino acid protein consisting of the same N-terminal region of NUP98 and a C-terminal region of 12 amino acids derived from a previously unidentified sequence. We isolated and characterized the chromosomal breakpoints. The breakpoint at 11p15 is mapped within a LINE repetitive element in a 9 kb intron of NUP98, and more than 60% of the sequenced 3 kb region surrounding the breakpoint junction consists of repetitive elements. The other breakpoint at 2q31 is in an intron of FN1, which is located 7 kb upstream of HOXD13, and the repetitive sequence content of the breakpoint junction is low. Local sequence duplications at genomic breakpoints suggest that the t(2;11) translocation is mediated through staggered double-strand DNA breaks. These results throw light on the mechanisms responsible for the generation of t(2;11) translocation and on the processes leading to t(2;11) leukemia.
Leukemia 2000 Sep
PMID:Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation. 1099 9


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