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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the key role of human homeobox (HOX) genes in development is well established, their function in adult cells is still under scrutiny. We have analyzed, in normal adult blood cell subpopulations, acute lymphoid leukemia (ALL) cells lines, and primary blasts, the RNA expression of all HOX-2 cluster genes (5'-2.5, 2.4, 2.3, 2.2, 2.1, 2.6, 2.7, 2.8, 2.9, 3') and nine genes in the HOX-1, -3, and -4 cluster by Northern blotting, RNAse protection, and/or reverse transcriptase polymerase chain reaction (RT-PCR). The analyzed HOX-1, -3, and -4 genes were never expressed in all tested cell populations. Natural killer (NK) cells activated in interleukin-2 (IL-2)/IL-1 beta-treated cultures exhibit a gradually increasing, abundant expression of three HOX-2 genes (2.2, 2.6, 2.8), while three other genes (2.3, 2.1, 2.7) are expressed at a lower level at late culture times. However, no HOX-2 gene is expressed in quiescent lymphocytes (NK, B and T [T-cell receptor (TCR) alpha/beta, gamma/delta lymphocytes, thymocytes] cells), granulocytes, and monocytes. In B- and T-ALL cell lines, HOX-2 genes are expressed according to different patterns: (1) widespread transcription (seven of nine genes, including 2.3 and 2.6) in the Peer line bearing the TCR gamma/delta; (2) expression of 2.5, 2.2, and 2.6 in the SEZ 627 line, which derives from an HTLV-1+ T-helper leukemia; (3) transcription of 2.3 and 2.6 in both the T-ALL CEM line and four B-ALL lines (interestingly, CALLA- B-ALL lines are constantly 2.3/2.6 RNA+); (4) no HOX-2 gene expression was detected in one T- and two B-ALL lines. Primary blasts from five T- and five pre-B-ALL showed selective expression of one or more HOX-2 genes, namely 2.5, 2.2, 2.6, and 2.7. Our data are compatible with the hypothesis that selected HOX-2 genes play a role in the IL-2/IL-1 beta-induced activation and/or proliferation of normal NK lymphocytes and possibly in the oncogenetic process of some T- and B-ALL.
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PMID:Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes. 135 62

Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2)-dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on patient mononuclear cells, the evidence of HTLV-I proviral integration sequences and the expression of HTLV-I genomic sequences in patient cells, indicates infection with HTLV-I and raises the possibility of an etiologic link between human retrovirus infection and some instances of large granular lymphocytic leukemia (T gamma-LPD).
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PMID:Human T cell leukemia virus-I-associated T-suppressor cell inhibition of erythropoiesis in a patient with pure red cell aplasia and chronic T gamma-lymphoproliferative disease. 289 60

A panel of 164 continuous human leukemia-lymphoma cell lines was analyzed for expression of c-kit using Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The c-kit transcripts were detectable in cell lines assigned to the myeloid (in 7 of 29 by Northern blotting and in 4 of 8 by RT-PCR), monocytic (in 1 of 24 by Northern blotting and in 3 of 6 by RT-PCR), erythroid (in 6 of 8 by Northern blotting and in 5 of 5 by RT-PCR), and megakaryoblastic (in 10 of 10 by Northern blotting) lineages, c-kit expression was not seen by Northern blotting or RT-PCR analysis in any of the 93 lymphoid leukemia, myeloma, or lymphoma cell lines. Treatment of four megakaryoblastic cell lines with protein kinase C activators (phorbol ester 12-O-tetradecanoylphorbol 13-acetate and Bryostatin 1) led to terminal differentiation as assessed by morphologic alterations, changes in the surface marker profile, and growth arrest. These effects were associated with enhanced c-kit mRNA expression. Exposure to all-trans retinoic acid down-regulated c-kit mRNA levels, while simultaneously causing morphologic alterations in all four cell lines. Stimulation with growth factors (interleukin-3, granulocyte macrophage-colony stimulating factor, and insulin-like growth factors I and II), used to assess any role of c-kit in proliferative processes, did not lead to significant upregulation or downregulation of c-kit expression. The finding of constitutive and high expression of c-kit mRNA in all megakaryoblastic leukemia cell lines and its modulation by various reagents might further contribute to the understanding of megakaryopoietic proliferation, differentiation, and leukemogenesis.
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PMID:c-kit expression in human megakaryoblastic leukemia cell lines. 751 41

We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.
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PMID:Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression. 778 Jan 55

Carboxylic esterases are widely distributed in hematopoietic cells. Monocytes express the esterase isoenzyme (termed 'monocyte-specific esterase', MSE) that can be inhibited by NaF in the alpha-naphthyl acetate cytochemical staining. We examined the expression of MSE in normal cells and primary and cultured leukemia-lymphoma cells. The MSE protein was demonstrated by isoelectric focusing (IEF); MSE mRNA expression was investigated by Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The following samples were positive for MSE protein and Northern mRNA expression: 20/24 monocytic, 4/32 myeloid, and 1/20 erythroid-megakaryocytic leukemia cell lines, but none of the 112 lymphoid leukemia or lymphoma cell lines; of the normal purified cell populations only the monocytes were positive whereas, T, B cells, and granulocytes were negative; of primary acute (myelo) monocytic leukemia cells (CD14-positive, FAB M4/M5 morphology) 14/20 were Northern mRNA and 11/14 IEF protein positive. RT-PCR revealed MSE expression in 29/49 Northern-negative lymphoid leukemia-lymphoma cell lines. The RT-PCR signals in monocytic cell lines were on average 50-fold stronger than the mostly weak trace expression in lymphoid specimens. On treatment with various biomodulators, only all-trans retinoic acid significantly upregulated MSE message and protein levels but could not induce new MSE expression in several leukemia cell lines; lipopolysaccharide and interferon-gamma increased MSE expression in normal monocytes. Analysis of DNA methylation with sensitive restriction enzymes showed no apparent regulation of gene expression by differential methylation; the MSE gene is evolutionarily conserved among mammalian species; the half-life of the human MSE transcripts was about 5-6 h. The extent of MSE expression varied greatly among different monocytic leukemia samples. However, the MSE overexpression in a significant number of specimens was not associated with gene amplification, gross structural rearrangements or point mutations within the cDNA region. Taken together, the results suggest that MSE expression is not absolutely specific for, but strongly associated with cells of the monocytic lineage; MSE is either not expressed at all or expressed at much lower levels in cells from other lineages. The biological significance, if any, of rare MSE messages in lymphoid cells detectable only by the hypersensitive RT-PCR remains unclear. Further studies on the regulation of this gene and on the physiological function of the enzyme will no doubt be informative with respect to its striking overexpression in some malignant cells and to a possible role in the pathobiology of monocytic leukemias.
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PMID:Characterization of the monocyte-specific esterase (MSE) gene. 809 31

Acute myeloid leukemia (AML) blast cells frequently produce interleukin-6 (IL-6) and other cytokines such as colony-stimulating factors (CSF: G-CSF, M-CSF, and GM-CSF), tumor necrosis factor (TNF)-alpha, and IL-1. The AML blast cells that produced IL-6 alone could not form autonomous in vitro colonies, whereas the blast cells that coexpressed CSF in addition to IL-6 were able to form such colonies. This suggests that IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blast cells. TNF-alpha and IL-1 that are produced from the blast cells may stimulate the growth of the AML blast cells by inducing production of CSF in bone marrow stromal cells or in the blast cell population itself. Improvement of clinical manifestations by the administration of an anti-IL-6 murine monoclonal antibody in a patient with AML-M5B confirmed an important role of IL-6 in in-vivo growth of the blast cells. The mRNA expression of IL-6 and its related genes in AML and acute lymphoid leukemia (ALL) blast cells was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-6 mRNA expression was common in AML, but rare in ALL, whereas the IL-6 receptor (IL-6R) mRNA was expressed in almost all cases of AML and in more than half of the cases of ALL. In contrast, gp130 was ubiquitously expressed in both AML and ALL. A significant correlation between the levels of IL-6R expression and the responsiveness of the blast cells to exogenous IL-6 was observed. This suggests the possibility of the rapid prediction of the responsiveness of leukemic cells to exogenous IL-6 (IL-6 administration for therapy) by rapid measurement of IL-6R mRNA by RT-PCR.
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PMID:The expression of IL-6 and its related genes in acute leukemia. 890 69

The tie gene encodes a receptor tyrosine kinase that together with its thus far unidentified ligand appears to play a distinct role in the regulatory pathway of early hematopoiesis and angiogenesis. Here, we attempted to define the possible involvement of tie in the pathobiology of hematopoietic malignancies by examining tie mRNA expression in human leukemia and lymphoma cells. We used a large panel of 93 well-characterized human continuous leukemia-lymphoma cell lines as model systems for the various hematopoietic cell lineages. At the Northern blot level, none of the 27 lymphoid leukemia or lymphoma-derived cell lines (originating from four B-precursor leukemia, four B-cell leukemia, four B-cell non-Hodgkin's lymphoma, two myeloma, two Burkitt lymphoma, four T-cell leukemia, five Hodgkin lymphoma, two anaplastic large cell lymphoma) tested expressed tie transcripts, whereas 23/42 (55%) of the myeloid cell lines analyzed expressed tie mRNA: in detail, 15 of 20 (75%) megakaryocytic, five of 11 (45%) erythroid, three of seven (43%) myelocytic and none of four monocytic cell lines were tie mRNA positive. In the reverse transcriptase-polymerase chain reaction analysis, which can detect very low levels of mRNA expression, all 12 myeloid cell lines and 19 of 39 (48%) lymphoid cell lines were positive. In experiments aimed at inducing cellular differentiation over an incubation period of 4 days, the phorbol ester PMA strongly enhanced tie mRNA expression in one erythroid and in one myelocytic cell line, but (like thrombopoietin) down-regulated tie mRNA expression in two megakaryocytic cell lines. Taken together these results indicate that tie is predominantly expressed in leukemia cells derived from the myeloid cell lineages (and here in particular in megakaryoblastic cells) and not in lymphoid leukemia cells. These observations provide some evidence for the hypothesis that tie is a receptor for a regulatory factor involved in normal and plausibly also leukemic hematopoiesis.
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PMID:Expression of tie receptor tyrosine kinase in human leukemia cell lines. 930 79

Alternative splicing of the human glucocorticoid receptor (hGR) primary transcript generates two receptor isoforms, hGRalpha and hGRbeta, with different carboxyl termini diverging at amino acid 727. By reverse transcriptase-polymerase chain reactions it was previously demonstrated that the hGRbeta message had a widespread tissue distribution. To demonstrate the presence of hGRbeta as protein we produced specific rabbit antisera to hGRbeta, as well as a hGRbeta-specific mouse monoclonal IgM antibody, by peptide immunizations. By SDS-polyacrylamide gel electrophoresis and Western immunoblotting we showed that hGRbeta is endogenously expressed at the protein level in HeLa cells and human lymphatic leukemia cells. Using an antibody directed against an epitope shared by both isoforms we showed a relatively lower expression of the hGRbeta form. We also showed that hGRbeta bound to hsp90 by immunoprecipitation of in vitro translated hGRbeta in reticulocyte lysate with hsp90-specific antibodies, a coprecipitation occurring also in the presence of dexamethasone. We could not demonstrate that hGRbeta inhibited the effects of dexamethasone-activated hGRalpha on a glucocorticoid-responsive reporter gene. In conclusion, low hGRbeta expression levels and hGRbeta-hsp90 interaction maintained in the presence of ligand and lack of inhibition of hormone-activated hGRalpha effects challenge the concept of the hGRbeta isoform as a proposed dominant negative inhibitor of hGRalpha activity.
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PMID:Evidence that the beta-isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor. 933 48

The t(9;22)(q34;q1 1) between the abl and bcr genes plays a pivotal role in the diagnosis and pathogenesis of chronic myelogenous leukemia (CML). Its detection is routinely accomplished by Southern blot analysis and karyotyping. Interphase fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) are emerging molecular techniques that offer viable alternatives. We analyzed 40 samples of peripheral blood and bone marrow (CML, 16; acute myelogenous leukemia, 6; acute lymphoblastic leukemia [ALL], 1; chronic lymphoblastic leukemia, 2; myelodysplasias, 4; myeloproliferative disorders, unclassified, 3; nonleukemic hematologic malignancies, 3; hypercellular bone marrow, 1; normal control samples, 2; and K562 cell line samples, 2) for the presence of bcr-abl fusion gene and its messenger RNA (mRNA) transcript by FISH and RT-PCR, respectively. We compared the results with results of Southern blot analysis and karyotyping when available. Cost analysis was performed. Thirty-three samples were evaluable by FISH; 14 of 14 evaluable CML samples and one ALL sample were positive for bcr-abl by FISH (100%). The other 15 evaluable samples were negative; 16 of 16 (100%) and 13 of 16 (81%) of CML cases were positive for bcr-abl mRNA by RT-PCR (chemiluminescent blot method) and RT-PCR (colorimetric method), respectively. The ALL sample was positive by both RT-PCR methods. All other samples were negative by RT-PCR (chemiluminescent blot method), and all but 1 case of myeloproliferative disorder tested negative by RT-PCR (colorimetric method). We conclude the utility of FISH and RT-PCR is associated with certain limitations, such as insufficient RNA for RT-PCR and the occasional absence of internal positive FISH control signals. However, each procedure offers (with a high concordance rate) a specific and cost-effective alternative to Southern blot analysis and karyotyping and improved turnaround time for the detection of bcr-abl fusion gene or its mRNA transcript.
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PMID:Comparative analysis of interphase FISH and RT-PCR to detect bcr-abl translocation in chronic myelogenous leukemia and related disorders. 942 10

Carboxyflavins were found to be potent selective inhibitors of Taq DNA polymerase in a polymerase chain reaction. The inhibitions were dose-dependent, and complete inhibitions were observed at the concentration of 3.0 microM. Carboxyflavins were much less, or not sensitive to the DNA polymerases tested such as calf thymus DNA polymerase alpha, rat DNA polymerase beta, human immunodeficiency virus type 1 reverse transcriptase, the Klenow Fragment of E. coli DNA polymerase I and T4 DNA polymerase. To our knowledge, there is no other report of an agent that selectively inhibits only a thermophilic polymerase. Interestingly, the carboxyflavins were able to prevent DNA synthesis in the murine lymphoid leukemia cell line L1210 in vitro; almost complete inhibitory levels were achieved in the range of less than 10 microM.
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PMID:Carboxyflavins, novel inhibitors of Taq DNA polymerase. 985 99


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