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)

One important question in stem cell biology of childhood acute lymphoblastic leukemia (ALL) is whether immature CD34+CD19- cells are part of the leukemic cell clone. CD34+CD19- cells from the bone marrow of 9 children with TEL/AML1-positive ALL were purified by flow sorting and subjected to reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence in situ hybridization, and methylcellulose cultures. In 3 of 8 patients analyzed by RT-PCR, no TEL/AML1-positive cells could be detected in the CD34+CD19- cell fraction. Altogether, the percentage of TEL/AML1-positive cells was low: 1.6% (n = 8; SD 2.2%) by nested real-time RT-PCR and 2.5% (n = 5; SD 2.6%) by fluorescence in situ hybridization. This correlated with the percentage of contaminating CD19+ leukemic cells in the CD34+CD19- cell fraction in 6 control sorts (mean 4.6%, SD 3.6%), indicating that the low levels of leukemic cells detected in the CD34+CD19- cell fraction could be attributed to sorter errors. Methylcellulose cultures in 3 patients provided further evidence that CD34+CD19- cells represent a candidate normal cell population. The clonogenicity of the CD34+CD19- cell fraction was similar to normal progenitors, including growth of primitive granulocyte, erythroid, macrophage, megakaryocyte colony-forming units. Each of 92 colonies from cultures with CD34+CD19- cells tested negative for TEL/AML1. In conclusion, our data support the hypothesis that the leukemia in TEL/AML1-positive childhood ALL originates in a CD19+ lymphoid progenitor. This has many therapeutic implications, eg, for purging of autologous stem cell products, flow cytometric monitoring of minimal residual disease, and targeting immunotherapy against the leukemic cell clone.
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PMID:Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal. 1209 59

A transcriptional repressor TEL belongs to the ETS family transcription factors and acts as a tumor suppressor. We identified five alternatively spliced TEL isoforms generated possibly through exon skipping mechanisms, by using reverse transcriptase-polymerase chain reaction analysis. Among them, we examined molecular and biological functions of a DeltaETS-TEL isoform (TEL-f). This isoform abrogated specific DNA-binding capacity to and trans-repressional ability through the ETS-binding site. Regardless, it showed dominant-negative effects over wild-type-TEL (TEL-a)-mediated transcriptional repression partly through sequestration of TEL-a from nucleus to cytoplasm. Moreover, TEL-f dominantly interfered with TEL-a-mediated erythroid differentiation in MEL cells and growth suppression in NIH3T3 cells. Interestingly, TEL isoforms without the entire (Delta exons 6+7-TEL) or a part (Delta exon 7-TEL) of ETS domain were expressed more frequently in myelodysplastic syndrome-derived leukemia than in myelodysplastic syndrome before transformation. This observation suggests that accumulation of the dominant-negative DeltaETS-TEL molecules could be a related phenomenon to leukemic progression of myelodysplastic syndrome.
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PMID:Functional analysis of a dominant-negative DeltaETS TEL/ETV6 isoform. 1509 86

The most common gene fusion (up to 25%) in childhood acute lymphoblastic leukemia (ALL) is that between ETV6 and RUNX1 (previously TEL and AML1, respectively; we here use the old nomenclature, for ease of reference to the literature). We determined the incidence of TEL/AML1 translocation with reverse transcriptase polymerase chain reaction (RT-PCR) and flow-cytometric immunophenotyping of newly diagnosed pediatric acute lymphoblastic leukemia patients in Thailand. The TEL/AML1 fusion genes were cloned into plasmids and sequenced. The variant found was confirmed with restriction fragment length polymorphism (RFLP) using SphI restriction endonuclease. Of 35 ALL patients, we found an incidence of 8.6% of TEL/AML1 translocation in ALL patients (12% of B-lineage ALL), which is lower than that reported in caucasians but is similar to that reported in Japanese and Koreans. All the translocation-positive patients had B-lineage common ALL, expressing CD10+. Interestingly, the two TEL/AML1 subclones were CD20 negative, and one subclone expressed a myelocytic marker (CD33+). Two TEL/AML1 subclones from bone marrow of ALL patients were isolated and sequenced. One was a wild type and the other was a variant having A --> G substitution at nucleotide 73 from the 5' end. The substitution nucleotide was located in the AML1 region. The clinical relevance of the variant is to be investigated.
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PMID:Cloning and sequencing of ETV6/RUNX1 (TEL/AML1) variant in acute lymphoblastic leukemia. 1510 90

The translocation t(12;22) involves MN1 and TEL and is rarely found in acute myeloid leukemia (AML). Recently, it has been shown in a mouse model that the fusion protein MN1-TEL can promote growth of primitive hematopoietic progenitor cells (HPCs) and, in cooperation with HOXA9, induce AML. We quantified MN1 expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 142 adult patients with AML with normal cytogenetics treated uniformly in trial AML-SHG 01/99. AML samples were dichotomized at the median MN1 expression. High MN1 expression was significantly correlated with unmutated NPM1 (P < .001), poor response to the first course of induction treatment (P = .02), a higher relapse rate (P = .03), and shorter relapse-free (P = .002) and overall survivals (P = .03). In multivariate analysis, MN1 expression was an independent prognostic marker (P = .02) in addition to age and Eastern Cooperative Oncology Group (ECOG) performance status. Excluding patients with NPM1(mutated)/FLT3ITD(negative), high MN1 expression was associated with shorter relapse-free survival (P = .057). MN1 was highly expressed in some patients with acute lymphoblastic but not chronic lymphocytic or myeloid leukemia. MN1 was highly expressed in HPCs compared with differentiated cells and was down-regulated during in vitro differentiation of CD34(+) cells, suggesting a functional role in HPCs. In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics.
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PMID:High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. 1691 23

A series of 92 Chinese children newly diagnosed with acute lymphoblastic leukemia (ALL) were examined for the ETV6-RUNX1 (previously TEL-AML1) fusion gene by using a nested reverse transcriptase-polymerase chain reaction. ETV6-RUNX1 fusion transcripts were detected in 21 of 92 patients (22.8%): 16 with common ALL, 4 with precursor B-cell ALL, and 1 with T-ALL. The prevalence of ETV6-RUNX1 positivity was 24.7% (20/81) in childhood B-lineage ALL. The prevalence of ETV6-RUNX1 in Chinese pediatric ALL patients proved to be similar to that found in other countries.
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PMID:Prevalence of ETV6-RUNX1 fusion gene in children with acute lymphoblastic leukemia in China. 1788 9

Chromosomal abnormalities are found in 80-90% of childhood cases of acute lymphoblastic leukemia (ALL). Leukemia-specific chromosome aberrations not only have prognostic value, but also provide important clues for further investigation into leukogenesis, leukemic cell transformation, and proliferation. This study used reverse transcriptase-polymerase chain reaction techniques to detect transcripts of the leukemia-specific chromosome fusion gene, TEL/AML1, and to monitor the expression levels of the TEL-AML1 fusion transcript in ALL patients at sequential intervals during their treatment course. Twenty-five ALL patients were enrolled, including 20 who were newly diagnosed and five in relapse. The incidence of the TEL/AML1 fusion gene in this study was 32%. The clinical features of our eight TEL/AML1-positive ALL cases were similar to those in other studies. Blotting analysis of the levels of the TEL-AML1 fusion transcript was used to detect minimal residual disease. Reduced levels of TEL/AML1 expression were found in four of the six patients whose bone marrow or peripheral blood samples were obtained after treatment. Further investigation with a larger sample size is warranted.
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PMID:TEL/AML1 fusion gene in childhood acute lymphoblastic leukemia in southern Taiwan. 1863 14

Acute lymphoblastic leukemia (ALL) accounts for approximately 80% of all acute leukemias during childhood. Chromosomal anomalies resulting from gene fusion, which are frequent in leukemias, create hybrid transcripts, the great majority of which encode transcription factors. We analyzed 88 pediatric patients (median age 7.3 years) who had B-lineage acute lymphoblastic leukemia (B-ALL), using reverse transcriptase-polymerase chain reaction, to look for gene fusion transcripts of TEL/AML1, E2A/PBX1, BCR/ABL p190, and MLL/AF4. The frequencies of these transcripts were 21.21, 9.68, 3.03, and 0%, respectively. All positive cases had a common B-ALL immunophenotype. The low frequency of the TEL/AML1 transcript that is found in developing countries, such as Brazil, may be due to the low incidence of leukemia; this would support Greaves' hypothesis.
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PMID:Molecular and chromosomal mutations among children with B-lineage lymphoblastic leukemia in Brazil's Federal District. 1944 Sep 70

Contemporary protocols ensure high-remission rate and long-term free survival in children with acute lymphoblastic leukemia (ALL), but small percentage of patients is still incurable. Molecular genetic methods helped to establish submicroscopic classification as well as minimal residual disease follow-up, considered to be responsible for relapse. Our study enrolled 70 pediatric patients with de novo ALL, analyzed using reverse transcriptase-polymerase chain reaction for the presence of four major risk-stratifying translocations (BCR/ABL, MLL/AF4, TEL/AML1, and E2A/PBX1). Bone marrow samples were collected at diagnosis, at the end of induction phase, and after intensive chemotherapy with the aim to establish the correlation between chromosomal aberration, clinical features, and treatment response. Presenting the results of this study, we offer another evidence of variable incidence and clinical characteristics of ALL subtypes.
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PMID:Clinical features of the most common fusion genes in childhood acute lymphoblastic leukemia. 1948 66

An international project was conducted to identify the common acute lymphoblastic leukemia (ALL)-specific fusion genes (ETV6-RUNX1,MLL-AF4,TCF3-PBX1, and BCR-ABL1) in developing countries to provide additional prognostic information at diagnosis. A total of 181 children with newly diagnosed ALL were tested by reverse transcriptase-polymerase chain reaction at laboratories in India, Pakistan, Myanmar, and Sudan, following a common protocol. To our knowledge, this report is novel in its report from these countries, except India. Across the four countries, the ETV6-RUNX1 (TEL-AML1) fusion gene was present in only 5% of cases. All the positive samples were from children aged 1 to 10 years, in whom the prevalence of this fusion gene, which is associated with good prognosis, was 7.4% (9 out of 121 samples), a much lower rate than reported from Western populations. In the 18 ALL cases tested in Sudan, a notable excess of MLL-AF4 (17%) and BCR-ABL1 (22%) fusion genes was found. This study highlights the need for wider international surveys of the molecular epidemiology of ALL.
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PMID:Distribution of common genetic subgroups in childhood acute lymphoblastic leukemia in four developing countries. 2062 May 98

The expression of drebrin, a cytoskeletal protein newly estimated by expression profiling to correlate with the genotype and prognosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), was examined by independent methods. After demonstrating its higher expression in TEL/AML1(pos) BCP-ALL by quantitative reverse transcriptase polymerase chain reaction, we developed an anti-drebrin monoclonal antibody (mAb). In a cohort of 86 children with BCP-ALL, we found increased expression of drebrin in TEL/AML1(pos) ALL. In conclusion, relationship of drebrin expression and prognosis or genotype can now be assessed using flow cytometry.
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PMID:High expression of cytoskeletal protein drebrin in TEL/AML1pos B-cell precursor acute lymphoblastic leukemia identified by a novel monoclonal antibody. 2149 2


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