Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to clarify the important association between eosinophilia-myalgia syndrome (EMS) and the L-tryptophan contaminant, "Peak E." To determine the functional activation of eosinophils induced by Peak E, eosinophil cationic protein (ECP) release was examined. Peak E augumented the release of ECP from peripheral blood normodense eosinophils by degranulation. Proliferative analysis using the human eosinophilic leukemia cell line EoL-3 showed prominent cellular replication in the presence of Peak E. Moreover, Peak E upregulated interleukin 5 (IL-5) receptor levels on normodense eosinophils. Of particular interest, Peak E-stimulated human splenic T cells produced bioactive and immunoreactive IL-5. Marked induction of IL-5 mRNA in Peak E-stimulated T cells was also shown by reverse-transcriptase polymerase chain reaction (RT-PCR). In contrast, L-tryptophan without the contaminant showed none of these effects. Thus, these data suggest that Peak E might be involved in the pathogenesis of EMS through bimodal mechanism including IL-5 generation by T cells and potentiation of eosinophil functional activation.
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PMID:1,1'-Ethylidenebis(tryptophan) (Peak E) induces functional activation of human eosinophils and interleukin 5 production from T lymphocytes: association of eosinophilia-myalgia syndrome with a L-tryptophan contaminant. 813 37

We assessed the origin of peripheral blood cells and bone marrow cells obtained from 15 patients after allogeneic bone marrow transplantation (allo BMT) by sensitive two-step polymerase chain reaction (PCR) amplification of MCT118, a variable number of tandem repeats regions (VNTR), that can be used to detect the DNA pattern of a minor cell population of only 1% without using radioisotopes. Mixed chimerism(MC) was detected in the haematopoietic cells of 3 patients. Two patients developed relapse of leukaemia after the detection of MC and one patient died of bone marrow hypoplasia 7 months after BMT. These findings indicate the clinical usefulness of this method to monitor patients with MC. Also, we analyzed cytokine gene expression in peripheral blood mononuclear cells during the development of graft-versus-host disease (GVHD) in patients who underwent allo BMT using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of interleukin(IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA was increased during the development of GVHD and the degree of this increment depended on the severity of the disease. These findings suggest that IL-1 beta, IL-6, and TNF-alpha produced by peripheral blood mononuclear cells play an important role in the development of GVHD. Therefore, analysis of MC and cytokine mRNA expression using the PCR technique after allogeneic bone marrow transplantation provide important information for treatment and monitoring of marrow transplant patients.
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PMID:[Clinical application of gene technology to monitor bone marrow transplantation]. 815 60

We previously isolated cDNA clones, MLL-a and MLL-b, derived from the 11q23 breakpoint region and detected gene rearrangements with MLL-b cDNA in infantile leukemia cell lines with 11q23 abnormalities. We also showed chimeric mRNAs between MLL and genes on partner chromosomes such as 4q21 and 19p13. In the present study, we isolated overlapping MLL cDNA clones of 11 kb and demonstrated that MLL-a and MLL-b were derived from the same gene, MLL/ALL-1/HRX. Northern analysis with an MLL cDNA probe detected different signals in t(11;19) cell lines, one being sized 10 kb in two cell lines, KOCL-33 and KOCL-44, and the other being 9.2 kb in the cell line, KOPN-1. To elucidate the molecular basis for the heterogeneity, we isolated cDNA clones of a translocation-associated gene on chromosome 19, LTG19, as well as chimeric cDNAs from KOPN-1. Northern analysis with LTG19 cDNA demonstrated the identical gene, encoding serine/proline rich 559 amino acid polypeptide, to be involved in all three cell lines. Sequence comparison revealed that the LTG19 portion of the predicted chimeric protein of KOPN-1 was fused in frame and contained the C-terminal 189 amino acids. This was shorter by 366 amino acids than those of KOCL-33 and KOCL-44, also fused in frame. Reverse transcriptase-PCR analysis demonstrated complex chimeric mRNAs in cell lines and leukemia samples. Although a chimeric mRNA of KOPN-1 type was rare, its presence suggested that the shared C-terminal portion of 189 amino acids of LTG19 contains important signal(s) for malignant transformation.
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PMID:Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) leukemia. 837 76

A human myeloid leukemia cell line, KBM-7, was developed from a patient in the blastic phase of chronic myeloid leukemia (CML). We characterized its morphology, immunophenotype, cytogenetics, and proliferative capacity. Developed in the absence of exogenous lymphokines, KBM-7 in vitro cloning capacity actually decreased when colony-stimulating factors were added. The cells had an aberrant immature myeloid phenotype, a doubling time of 22 h in suspension cultures and a high cloning efficiency in semisolid system (24 +/- 3)%. Early passages contained one near-haploid (predominant) and one hyperdiploid stem line. Gradually the hyperdiploid stem line became predominant, reaching an average of 49 chromosomes per cell. Cells from passage 89 had two Philadelphia chromosomes [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Detailed molecular characterization of the breakpoint in the t(9;22)(q34;q11) revealed that KBM-7 had the BCR 2/ABL II splice junction. The cells had high protein kinase (p210BCR-ABL) activity and carried two identified variants of an ABL-BCR message. There was no evidence that normal BCR or c-ABL messages were expressed, assessed with the reverse-transcriptase polymerase chain reaction. When KBM-7 cells were heterotransplanted into nude mice without immunosuppressive pretreatment, one of three mice injected with 1 x 10(7) cells and all mice injected with 1 x 10(8) cells developed slowly growing granulocytic sarcomas within 6-8 weeks. These tumors were locally invasive but did not metastasize. We conclude that the KBM-7 cell line will be of value for investigating molecular events underlying neoplastic transformation in CML, in particular for studying the effects of BCR-ABL and ABL-BCR on the proliferation of CML cells in the absence of normal BCR and c-ABL messages.
Leukemia 1995 Dec
PMID:KBM-7, a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c-ABL and BCR transcripts. 860 23

Reverse transcriptase-polymerase chain reaction is a recent technique in the diagnosis and assessment of minimal residual disease of acute promyelocytic leukemia, by amplification, of the different PML-RARalpha transcripts resulting from the t(15;17) translocation. The main issues addressed by the Second Workshop on PML-RARalpha-RT-PCR which took place in Paris, France on 17-18 December 1994, were related to (1) defining the specific pitfalls of the PML-RARalpha-RT-PCR, and means to improve the sensitivity of the technique; (2) the validity of PCR results obtained in CR to provide information on the extent of the disease; (3) the frequency and prognostic value of the different PML-RARalpha transcripts.
Leukemia 1996 Feb
PMID:RT-PCR in acute promyelocytic leukemia: second workshop of the European Retinoic Group, Paris, France, 17-18 December 1994. 863 50

The t(6;11)(q27;23) is one of the most common translocations observed in patients with acute myeloid leukemia (AML). The translocation breakpoint involves the MLL gene, which is the human homolog of the Drosophila trithorax gene, at 11q23 and the AF6 gene at 6q27. Reverse transcriptase-polymerase chain reaction (RT-PCR) using an MLL sense primer and an AF6 antisense primer detected the MLL/AF6 fusion cDNA from three leukemia patients with the t(6;11) [two AML and one T-acute lymphoblastic leukemia (ALL)] and one cell line. The fusion point in the AF6 cDNA from these cases is identical, regardless of the leukemia phenotype. The ML-2 cell line, which was established from a patient with AML that developed after complete remission of T-cell lymphoma, has retained an 11q23-24 deletion from the lymphoma stage and has acquired the t(6;11) with development of AML. The ML-2 cells have no normal MLL gene on Southern blot analysis, which indicates that an intact MLL gene is not necessary for survival of leukemic cells.
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PMID:Analysis of the t(6;11)(q27;q23) in leukemia shows a consistent breakpoint in AF6 in three patients and in the ML-2 cell line. 870 46

Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the formation of a chimeric mRNA transcript. We describe a patient with acute myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric transcript. Reverse transcriptase polymerase chain reaction and the sequencing of its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201. To our knowledge, this is the first report of an AML (M1) case with del(16) and CBFB/MYH11 rearrangement.
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PMID:CBFB/MYH11 fusion transcripts in a case of acute myelogenous leukemia (M1) with partial deletion of the long arm of chromosome 16. 873 92

Met-ase-1 is a 30 000 Mr serine protease (granzyme) that was first isolated in the cytolytic granules of rat CD3(-) large granular lymphocytes. We screened a mouse genomic library with rat Met-ase-1 cDNA, and obtained bacteriophage clones that contained the mouse Met-ase-1 gene. The mouse Met-ase-1 gene comprises five exons spanning approximately 5.2 kilobases (kb) and exhibits a similar structural organization to its rat homologue and a family of neutrophil elastase-like serine proteases. Mouse Met-ase-1 mRNA was only detected in total cellular and poly A mRNA of mouse CD3(-) GM1(+) large granular lymphocytes derived from splenocytes stimulated with IL-2 and the mouse NK1.1(+) cell line 4 - 16. Spleen T-cell populations generated by Concanavalin A stimulation and a number of mouse pre-NK and T cell lines did not express mouse Met-ase-1 mRNA. The 5' flanking region of the mouse Met-ase-1 gene also shares considerable regions of identity with the 5' flanking region of the rat Met-ase-1 gene. A 3.3 kb segment of 5' sequence flanking the mouse Met-ase-1 gene was inserted upstream of the chloramphenicol acetyltransferase reporter gene and this construct transiently transfected into a variety of mouse and rat large granular lymphocyte leukemia and T-cell lines. The transcriptional activity of the mouse Met-ase-1 5' flanking region was significant in the RNK-16 large granular lymphocyte leukemia, strongest in the 4 - 16 mouse NK1.1(+) cell line, and weak in several mouse pre-NK cell lines. Reverse transcriptase polymerase chain reaction of mouse large granular lymphocyte mRNA was used to derive the full-length coding sequence for mouse Met-ase-1. The predicted hexapropeptide of mouse Met-ase-1 (Asn-6 to Gln-1), was deleted by polymerase chain reaction mutagenesis to enable expression of active mouse Met-ase-1 in mammalian COS-7 cells. Northern blot analysis and protease assays of transfected COS cell lysates against a panel of thiobenzyl ester substrates formally demonstrated that the mouse Met-ase-1 gene encodes a serine proteinase that hydrolyzes substrates containing a long narrow hydrophobic amino acids like methionine, norleucine, and leucine in the P1.
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PMID:Cloning and expression of the recombinant mouse natural killer cell granzyme Met-ase-1. 878 Nov 19

Reverse transcriptase must perform two specialized template switches during retroviral DNA synthesis. Here, we used Moloney murine leukemia virus-based vectors to examine the site of one of these switches during intracellular reverse transcription. Consistent with original models for reverse transcription, but in contrast to previous experimental data, we observed that this first strand transfer nearly always occurred precisely at the 5' end of genomic RNA. This finding allowed us to use first strand transfer to study the classes of errors that reverse transcriptase can and/or does make when it switches templates at a defined position during viral DNA synthesis. We found that errors occurred at the site of first strand transfer approximately 1000-fold more frequently than reported average reverse transcriptase error rates for template-internal positions. We then analyzed replication products of specialized vectors that were designed to test possible origins for the switch-associated errors. Our results suggest that at least some errors arose via non-templated nucleotide addition followed by mismatch extension at the point of strand transfer. We discuss the significance of our findings as they relate to the possible contribution that template switch-associated errors may make to retroviral mutation rates.
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PMID:Determination of the site of first strand transfer during Moloney murine leukemia virus reverse transcription and identification of strand transfer-associated reverse transcriptase errors. 904 14

Receptor tyrosine kinases (RTK) play an important role in the signal transduction of normal and malignant cells. There are different families of RTKs which are mainly characterized by differences in the ligang-binding extracellular domains. Axl (or UFO/Ark) is the first member of a new class of RTK with two fibronectin type III domains and two immunoglobulin-like domains present at the extracellular domain. The axl-gene has been isolated by means of gene transfection studies using DNA of patients with chronic myelogeneous leukemia. For a previous and the present study, we used a sensitive reverse-transcriptase polymerase chain reaction assay to detect axl's mRNA in cells from normal and malignant hematopoietic tissue. Axl's mRNA expression was mainly detected in myelo-monocytic cells, whereas much weaker transcription was seen in lymphatic cells and in lymphatic leukemias. In normal bone marrow, axl was heavily transcribed in marrow stromal cells. Further, we analysed Axl protein expression using monoclonal antibody M50 in peripheral stem cell harvests; in most harvests, no co-expression of CD34 and Axl was detected. However, in one patient with AML in complete remission, Axl was co-expressed on 80% of the CD34-positive population. These data show that axl is preferentially expressed in monocytes and stromal cells. Furthermore, a fraction of CD34-positive progenitor cells may express Axl. The exact mechanism for transformation of myeloid progenitor cells through Axl, however, remains to be determined.
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PMID:Recent progress on the role of Axl, a receptor tyrosine kinase, in malignant transformation of myeloid leukemias. 913 Jun 17


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