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)

In acute myeloblastic leukemia (AML) the follow-up of minimal residual disease (MRD) has focused on specific chromosomal aberrations (e.g. t(15;17), t(8;21), inv16/t(16;16)) mostly employing reverse transcriptase-PCR. High or increasing levels of MRD are associated with an increased risk of relapse but low levels may persist in patients with prolonged or even durable remission. In adult patients with AML the increased risk of relapse has also been demonstrated using flow cytometry and fluorescence in situ hybridization (FISH). We evaluated the presence of MRD among pediatric patients with AML during and after the cessation of therapy. We were able to establish a clonal marker for the follow-up in 80% of our cases; 11 of the 15 with a clonal marker had detectable MRD at some point during follow-up while 4/15 relapsed 12-14 months after diagnosis. In two there was hematological relapse preceded by an increase in their FISH-detectable number of clonal cells. In 7 of the 11 remaining in CR1 there were small (< 1%) numbers of clonal cells detectable at one or more time-points. Out of the group of 15 pediatric patients with AML, 12 are currently alive in CCR with a median follow-up of 44 months (range 7-63 months). Our data establish the role of metaphase-FISH in the follow-up of AML in children and emphasize the importance of an increasing level of MRD in predicting a relapse. Yet, low and stable levels of marrow MRD a ppear compatible with CCR.
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PMID:Follow-up of minimal residual disease in pediatric acute myeloblastic leukemia using metaphase-FISH. 1215 94

Most active non-LTR (long terminal repeat) retrotransposons carry two open reading frames (ORFs) encoding ORF1p and ORF2p proteins. The ORF2p proteins are relatively well studied and are known to contain endonuclease/reverse transcriptase domains. At the same time, the biological function of ORF1p proteins remains poorly understood, except in that they nonspecifically bind single-stranded mRNA/DNA molecules. CR1-like elements form the most widely distributed clade/superfamily of non-LTR retrotransposons. We found that ORF1p proteins encoded by diverse CR1-like elements contain conserved esterase domain (ES) or plant homeodomain (PHD). This indicates that CR1-like ORF1p proteins are either lipolytic enzymes or are involved in protein-protein interactions related to chromatin remodeling. Sequence conservation of ES suggests that interaction with cellular membranes is an important phase in life circles of CR1-like elements. Presumably such interaction helps in penetrating host cells. As a consequence, the presence of multiple young CR1 families characterized by approximately 10% intrafamily and 40% interfamily identities may be explained by a relatively frequent horizontal transfer of these CR1-like elements. Unexpectedly, ES links together non-LTR retrotransposons and single-stranded RNA viruses like influenza C and coronaviruses, which are known to depend on their own ES.
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PMID:The esterase and PHD domains in CR1-like non-LTR retrotransposons. 1251 4

BfCR1 is the first non-long terminal repeat retrotransposon to be characterised in the amphioxus genome. Sequence alignment of the predicted translation product reveals that BfCR1 belongs to the CR1-like retroposon class, a family widely distributed in vertebrate and invertebrate lineages. Structural analysis shows conservation of the specific motifs of the ORF2-CR1 elements: the N-terminal endonuclease, the reverse transcriptase and the C-terminal domains. The BfCR1 element possesses an atypical 3' terminus consisting of the tandem repeat (AAG)6. We gathered evidence supporting the mobility of this element and report an estimated 15 copies of BfCR1, mostly truncated, per haploid genome, a remarkably low number when compared to that of vertebrates. Phylogenetic analysis, including the amphioxus element, seems to indicate that (i) CR1-like retroposons cluster in a monophyletic group and (ii) the CR1-like family was already present in the chordate ancestor. Our data provide further support for the horizontal transmission of CR1-like elements during early vertebrate evolution.
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PMID:The first non-LTR retrotransposon characterised in the cephalochordate amphioxus, BfCR1, shows similarities to CR1-like elements. 1278 27

Over a hundred families of non-long terminal repeat retrotransposons (non-LTRs) were found in the newly released Anopheles gambiae genome assembly during a reiterative and comprehensive search using the conserved reverse transcriptase (RT) domains of known non-LTRs as the starting queries. These families, which are defined by at least 20% amino acid sequence divergence in their RT domains, range from a few to approximately 2,000 copies and occupy at least 3% of the genome. In addition to having an unprecedented number of diverse families, A. gambiae non-LTRs represent 8 of the 15 previously defined clades plus two novel clades, Loner and Outcast, more than what has been reported for any genome. Five families were found belonging to the L1 clade, which had no invertebrate representatives to date. One unique family named Sponge contains only a complete open reading frame (ORF) for the Gag-like protein and appears to have been mobilized by a family of the CR1 clade. Although most families appear to be inactive as expected, all clades except R4 have families with characteristics suggesting recent activity. At least 21 families have multiple full-length copies with over 99% nucleotide identity and some or all of the following characteristics: target site duplications (TSDs), intact ORFs, and corresponding expressed sequence tags (ESTs). The incredible diversity and the maintenance of multiple recently active lineages within different clades indicate a complex evolutionary scenario. A. gambiae non-LTRs have the potential to be developed as tools for population genetic studies and genetic manipulations of this primary vector of the devastating disease malaria. The semi-automated reiterative search approach described here may be used with any genome assembly to systematically survey and characterize non-LTRs as well as other transposable elements that encode a conserved protein.
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PMID:Non-LTR retrotransposons in the African malaria mosquito, Anopheles gambiae: unprecedented diversity and evidence of recent activity. 1283 32

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of a broad spectrum of autoantibodies against nuclear, cytoplasmic and cell surface antigens and immune complex overload. Complement receptor 1 (CR1, CD 35), a transmembrane glycoprotein found on the surface of erythrocytes, leukocytes and glomerular podocytes plays a key role in the clearance of immune complexes and regulation of complement cascade. A drastic decline in the level of cell surface CR1 appears to be an important event in pathology of SLE. However, the etiology of lower than normal expression of cell surface CR1 in this disease is poorly understood. We studied the level of leukocyte CR1 transcription in 30 patients with active SLE and 30 controls by reverse transcriptase-polymerase chain reaction (RT-PCR) and related the same with the level of CR1 protein expression monitored by Western blotting. For RT-PCR, ratio of CR1/beta-actin was considered for semiquantitation of the level of CR1 transcription. Despite individual variation at the level of transcription, 70% (21 out of 30) of the patients expressed CR1 transcript at the lowest range of 0-15% as compared to the controls wherein only 30% (9 out of 30 individuals) demonstrated CR1 transcript in this range. Majority of the controls (70%) expressed CR1 transcript at the level above 15%. Mean level of CR1 transcript in patients (mean +/- S.D. = 21.09 +/- 14.3) was significantly lower than the controls (mean +/- S.D. = 48.91 +/- 26.34) (P < 0.001). The level of CR1 transcription correlated inversely with circulating immune complexes (CIC) (r = 0.52, P < 0.01). This may suggest that although erythrocyte CR1 is the chief vehicle for CIC clearance, drastic decline in leukocyte CR1 expression may impair the phagocyte mediated immune complex clearance and contribute to increased complement consumption in SLE. Total leukocyte CR1 protein expression was also significantly reduced in patients (P < 0.001) as compared to controls. This decline at the protein level gave a very significant positive correlation with CR1 transcript (r = 0.67, P < 0.01). A marginal increase in soluble CR1 (sCR1) was observed in the plasma (ELISA) of SLE patients compared to the controls but was insignificant. This paper for the first time brings evidence to suggest that reduced synthesis of CR1 contributes substantially to the low cell surface CR1 expression in SLE. Our findings also suggest increased proteolytic cleavage of leukocyte cell surface CR1 in these patients. However, evidence for the latter is indirect.
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PMID:Reduced complement receptor 1 (CR1, CD35) transcription in systemic lupus erythematosus. 1516 41

Association of long-term clinical remission and molecular disease-eradication is well established in acute myeloid leukemia (AML) patients with t(15;17) and inv(16). In patients with t(8;21) positive AML no consensus exists over the disappearance of the AML1/ETO fusion transcript during the course of disease and most studies reported reverse transcriptase polymerase chain reaction (RT-PCR) positivity as a common finding after consolidation chemotherapy, autologous and allogeneic stem cell transplantation (alloSCT). In our single center study, we performed RT-PCR monitoring in 14 patients with t(8;21) in CR1 (n = 13) and/or CR2 (n = 4). The median number of bone marrow (BM) and/or peripheral blood (PB) samples per patient was 18 (range, 2-43). In 5 out of 6 cases relapse occurred after persistence of minimal residual disease (MRD) in CR for 4-14 months. The sixth patient relapsed despite molecular remission (MR) in BM and PB for 3 months, molecular relapse preceded hematological relapse for 7 months. Eleven patients with a median follow-up of 7.8 (range, 1.5-15.4) years are in persistent CR and MR after consolidation chemotherapy (n = 7). mainly with repetitive cycles of high-dose Ara-C, autologous (n = 1) or myeloablative allogeneic (n = 3) stem cell transplantation. Molecular remission was attained immediately after alloSCT, but after 6-26 months in CR in patients with consolidation chemotherapy. In 7 patients, MRD was only studied in long-term remission. In conclusion, long-term CR was associated with persistent molecular disease-eradication. In our patients, molecular remission was a prerequisite but not a guarantee for long-term disease-free survival. Hematological relapse never occurred without prior molecular relapse. Due to the slow kinetics of AML1/ETO after consolidation chemotherapy the value of qualitative RT-PCR to predict early relapse is limited. In this situation quantitative RT-PCR might help to define individual relapse risk and to improve as well as facilitate clinical decision-making.
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PMID:Molecular disease eradication is a prerequisite for long-term remission in patients with t(8;21) positive acute myeloid leukemia: a single center study. 1529 57

We screened across the taxonomic diversity of order Scorpiones (22 species belonging to 21 genera and 10 families) for the presence of seven different clades of non-LTR retrotransposons in their genomes using PCR with newly designed clade-specific consensus-degenerate hybrid oligonucleotide primers. Scorpion genomes were found to contain four known non-LTR retrotransposon clades: R1, I, Jockey, and CR1. In total, 35 fragments of reverse transcriptase genes of new elements from 22 scorpion species were obtained and analyzed for three clades, Jockey, I, and CR1. Phylogenies of different clades of elements were built using amino acid sequences inferred from 33 non-LTR retrotransposon clones. Distinct evolutionary lineages, with several major groups of the non-LTR retroelements were identified, showing significant variation. Four lineages were revealed in Jockey clade. The phylogeny of I clade showed strong support for the monophyletic origin of such group of elements in scorpions. Three separate lineages can be distinguished in the phylogenetic tree of CR1 clade. The large fraction of the isolated elements appeared to be defective.
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PMID:Divergent non-LTR retrotransposon lineages from the genomes of scorpions (Arachnida: Scorpiones). 1632 71

Long interspersed elements (LINEs) are a type of retroposon and are widely distributed in most eukaryotic genomes. LINEs are classified into two groups, the stringent type and relaxed type, based on the recognition of the 3' tail of their own RNA by reverse transcriptase (RT) during retrotransposition. Although most LINEs are thought to belong to the stringent type, retrotransposition studies of the stringent type LINEs are relatively limited compared with those of the relaxed type. We have now isolated two retrotransposition-competent LINEs (ZfL2-1 and ZfL2-2) from the zebrafish genome. Both ZfL2-1 and ZfL2-2 are members of the L2 clade; ZfL2-1 encodes two open reading frames (ORFs) and ZfL2-2 encodes one ORF, and each of the ORFs is required for retrotransposition. Using a retrotransposition assay in HeLa cells, we established that both ZfL2-1 and Zfl2-2 belong to the stringent type. We also demonstrated that an esterase (ES) domain encoded by ZfL2-1 ORF1 strongly enhances its own retrotransposition. The ES domain is encoded only in ORF1 of LINEs classified in the CR1 and L2 clades, although its function or significance in retrotransposition has not been elucidated. Thus, this is the first experimental evidence that the ES domain has an enhancing function during retrotransposition. These zebrafish LINEs will be useful for determining the function of ORF1 and the retrotransposition mechanism of stringent-type LINEs.
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PMID:Isolation and characterization of retrotransposition-competent LINEs from zebrafish. 1635 61

Despite recent advances in the treatment of acute promyelocytic leukemia (APL), early mortality and relapses still occur. With the view to evaluate the role of FLT3 mutation in APL, 54 patients (median age 28 years, range11-57 years, male to female ratio 1.2:1, median TLC 8.4 x 10(9)/l, range 1-170 x 10(9)/l) were studied by reverse transcriptase-PCR. Forty-two patients (77%) achieved first remission (CR1). Ten (18.5%) of the 54 patients had internal tandem duplication of exons 11 and 12 of the FLT3 gene. The median TLC count was significantly higher in FLT3 positive cases (Median TLC 55.0 x 10(9)/l) as compared to FLT3 negative cases (Median TLC 6.8 x 10(9)/l) (p = 0.001). Induction CR was much lower (40%) in FLT3/ITD positive cases as compared to 86% of FLT3/ITD negative cases (p = 0.005). Early deaths too were significantly associated with FLT3/ITD positive cases (50 vs. 16% p = 0.033). The difference in the occurrence of bcr1 and bcr3 isoforms was not statistically significant between the two groups. The data suggest that the presence of FLT3/ITD in APL patients confers a poor prognosis.
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PMID:Impact of FLT3 internal tandem duplications on Indian acute promyelocytic leukemia patients: prognostic implications. 1745 89

Retrotransposons encompass a specific class of mobile genetic elements that are widespread across eukaryotic genomes. The impact of the varied types of retrotransposons on these genomes is just beginning to be deciphered. In a step towards understanding their role in litopenaeid shrimp, we have herein identified nine non-LTR retrotransposons, among which several appear to exist outside the standard defined clades. Two Litopenaeus stylirostris elements were discovered through degenerate PCR amplification using previously defined non-LTR degenerate primers, and through primers designed from a RAPD-derived sequence. A third genomic L. stylirostris element was identified using specific priming from an amplification protocol. These three PCR-derived sequences showed conserved domains of the non-LTR reverse transcriptase gene. In silico searching of genome databases and subsequent contig construction yielded six non-LTR retrotransposons (both genomic and expressed) in the Litopenaeus vannamei genome that also exhibited the highly conserved domains found in our PCR-derived sequences. Phylogenetic placement among representatives from all non-LTR clades showed a possibly novel monophyletic group that included five of our nine sequences. This group, which included elements from both L. stylirostris and L. vannamei, appeared most closely related to the highly active RTE clade. Our remaining four sequences placed in the CR1 and I clades of retrotransposons, with one showing strong similarity to ancient Penelope elements. This research describes three newly discovered retrotransposons in the L. stylirostris genome. Phylogenetic analysis clusters these in a monophyletic grouping with retrotransposons previously described from two closely related species, L. vannamei and Penaeus monodon.
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PMID:Evidence of multiple retrotransposons in two litopenaeid species. 1855 73


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