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)

The 8;21 translocation is one of the most common chromosomal translocations in acute myelogenous leukemia (AML), accounting for 40% of pediatric AML with French-American-British (FAB)-M2 morphology. The chromosomal breakpoints have recently been identified at the molecular level and shown to involve the AML1 gene on chromosome 21 and the ETO gene on chromosome 8. Translocation results in the consistent fusion of these genes on the der(8) chromosome, resulting in the production of a novel chimeric gene and message. Using oligonucleotide primers derived from the AML1 and ETO cDNAs, we were able to amplify a specific fusion transcript from 26 of 26 patients with t(8;21) by a reverse transcriptase polymerase chain reaction (PCR) approach. DNA fragments of identical size were generated from each case including two with complex translocations. Studies on the sensitivity and specificity of this approach show that PCR analysis can be used as a rapid, accurate, and sensitive means for detecting this chromosomal abnormality, and for following the patients' response to therapy.
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PMID:An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation. 849 24

We examined mRNA expression and internal tandem duplication of the Fms-like tyrosine kinase 3 (FLT3) gene in haematological malignancies by reverse transcriptase-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing. By RT-PCR, expression of FLT3 was detected in 45/74 (61%) leukaemia cell lines and the frequency of expression of FLT3 was significantly higher in undifferentiated type (B-precursor acute lymphoblastic leukaemia; ALL) than in differentiated type cell lines (B-ALL) (P = 0.0076). Using the genomic PCR method, 194 fresh samples including 87 acute myeloid leukaemias, 60 ALLs, 32 myelodysplastic syndromes (MDSs) and 15 juvenile chronic myelogenous leukaemias (JCMLs) were examined. Tandem duplication was found in 12 (13.8%) AMLs and two (3.3%) ALLs. Sequence analyses of the 14 samples with the duplication revealed that eight showed a simple tandem duplication and six a tandem duplication with insertion. Most of these tandem duplications occurred within exon 11, and two duplications occurred from exon 11 to intron 11 and exon 12. No tandem duplications of FLT3 gene were detected in MDS or JCML. The frequency of tandem duplication of FLT3 gene in childhood AML was lower than that in adult AML so far reported. All of the 12 AML patients with the duplication died within 47 months after diagnosis, whereas two ALL patients with the duplication have survived 44 and 72 months, respectively. These two ALL patients expressed both lymphoid and myeloid antigens and were considered to have biphenotypic leukaemia. These results suggest that tandem duplication is involved in ALL in addition to AML, but not in childhood MDS or JCML, and that childhood AML patients with the tandem duplication have a poor prognosis.
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PMID:Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. 1023 79

To determine the incidence of leukemia-specific rearrangements, 60 cases of childhood acute myeloblastic leukemia and transient myeloproliferative disorder were screened with a novel multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and the results were correlated with the cytogenetic findings. The RT-PCR assay detects 28 different fusion genes and more than 80 different fusion transcript variants. RNA was isolated from methanol/acetic acid-fixed cells that had been routinely prepared for cytogenetic analysis. Nine different fusion transcripts were found in 40% of the cases, whereas 78.3% of the cases had abnormal karyotypes. Two cases with a t(6;11) and an MLL/AF6 gene fusion were missed cytogenetically. Conversely, cytogenetic analysis revealed 10 other well-defined chromosome rearrangements. Although cytogenetic analysis reveals a much broader range of abnormalities, multiplex RT-PCR serves as quality control and provides the essential information for minimal residual disease studies. Moreover, discrepant findings lead to the detection of new rearrangements on the molecular genetic level.
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PMID:Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia. 1115 1

The recurrent translocation t(5;11)(q35;p15.5) associated with a 5q deletion, del(5q), has been reported in childhood acute myeloid leukemia (AML). We report the cloning of the translocation breakpoints in de novo childhood AML harboring a cryptic t(5;11)(q35;p15.5). Fluorescence in situ hybridization (FISH) analysis demonstrated that the nucleoporin gene (NUP98) at 11p15.5 was disrupted by this translocation. By using 3'--rapid amplification of complementary DNA ends (3'-RACE) polymerase chain reaction, we identified a chimeric messenger RNA that results in the in-frame fusion of NUP98 to a novel gene, NSD1. The NSD1 gene has 2596 amino acid residues and a 85% homology to the murine Nsd1 with the domain structure being conserved. The NSD1 gene was localized to 5q35 by FISH and is widely expressed. The reciprocal transcript, NSD1-NUP98, was also detected by reverse transcriptase--polymerase chain reaction. This is the first report in which the novel gene NSD1 has been implicated in human malignancy. (Blood. 2001;98:1264-1267)
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PMID:A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. 1182 62

The identification of specific chromosome abnormalities in acute myeloid leukemia (AML) is important for the stratification of patients into the appropriate treatment protocols. However, a significant proportion of diagnostic bone marrow karyotypes in AML is reported as normal by conventional cytogenetic analysis and it is suspected that these karyotypes may conceal the presence of diagnostically significant chromosome rearrangements. To address this question, we have developed a novel 12-color fluorescence in situ hybridization (FISH) assay for telomeric rearrangements (termed M-TEL), which uses an optimized set of chromosome-specific subtelomeric probes. We report here the application of the M-TEL assay to 69 AML cases with apparently normal karyotypes or an isolated trisomy. Of the 69 cases examined, 3 abnormalities were identified, all in the normal karyotype group. The first was a t(11;19)(q23;p13), identified in an infant with AML-M4. In 2 other young patients with AML (< 19 years), an apparently identical t(5;11)(q35;p15.5) was identified. Breakpoint mapping by FISH and reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed that this was the same t(5;11) as previously identified in 3 children with AML, associated with del(5q) and resulting in the NUP98-NSD1 gene fusion. The t(5;11) was not detected by 24-color karyotyping using multiplex FISH (M-FISH), emphasizing the value of screening with subtelomeric probes for subtle translocations. This is the first report of the t(5;11)(q35;p15.5) in association with an apparently normal karyotype, and highlights this as a new, potentially clinically significant chromosome rearrangement in childhood AML.
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PMID:A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay. 1293 34

The expression of the PRAME gene (preferentially expressed antigen of melanoma) was measured by quantitative reverse transcriptase polymerase chain reaction in 50 children with newly diagnosed acute myeloid leukemia (AML), three samples of CD34(+) stem cells, six bone marrow samples, and 10 peripheral blood samples of healthy donors, as well as three AML cell-lines (KG-1, U937, and HL-60). Eight patients were also analyzed in relapse. Contrary to previous reports, we could show that the PRAME gene is expressed by CD34(+) stem cells. This might constitute a problem in using PRAME for tumor immunotherapy. Overexpression of PRAME was found in 62% (n=31) of our patients. The rates of overall and disease-free survival in this group were higher than in patients with no or low expression (P<0.05). PRAME expression was negatively correlated to the white blood cell count at diagnosis (P<0.05) and significantly higher in patients with t(8;21). The levels of expression at diagnosis corresponded with those at relapse (P<0.001) and increased levels could be found prior to the relapse in one patient who was regularly monitored. Our results suggest that the expression of PRAME is an indicator of favorable prognosis and could be a useful tool for monitoring minimal residual disease in childhood AML.
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PMID:Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. 1194 37

The AF1q gene, a mixed-lineage leukemia fusion partner, is highly expressed in hematopoietic progenitor cells but has low expression in differentiated cells. We determined the expression of the AF1q gene by reverse transcriptase-polymerase chain reaction in 64 pediatric acute myeloid leukemia (AML) patients treated on Children's Cancer Group clinical trial CCG-2891 and correlated its expression level to clinical characteristics and outcome. AF1q expression in patients varied from 0- to 154-fold compared with normal marrow, and increasing expression level was associated with worsening survival, with a hazard ratio of 1.02 per fold increase in AF1q expression (P = .032). We divided patients into tertile groups based on AF1q expression level. Patients with high AF1q expression (top tertile) had a higher predominance of French-American-British M1 compared to patients with lower 2 tertiles of AF1q expression (43% vs 9%, P = .003). High AF1q expression was associated with poor survival in univariate and multivariate models. Overall survival at 8 years for patients with the high AF1q expression was 19% versus 50% in patients with low AF1q expression, (P = .01). AF1q expression may correlate with clinical outcome in pediatric AML, although it is not clear if AF1q is simply a marker of a more primitive phenotype or contributes directly to leukemogenesis.
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PMID:Elevated expression of the AF1q gene, an MLL fusion partner, is an independent adverse prognostic factor in pediatric acute myeloid leukemia. 1521 37

The rare t(9;11)(p22;p15) translocation is associated with adult acute myeloid leukemia (AML) with immature forms. We report a novel fusion of the NUP98 and LEDGF genes in a pediatric AML with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes exhibiting the same chromosomal rearrangement. Fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR) studies identified the chimeric transcript product of in-frame fusion of NUP98 exon 8 to LEDGF exon 4.
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PMID:t(9;11)(p22;p15) with NUP98-LEDGF fusion gene in pediatric acute myeloid leukemia. 1572 83

The characterization of leukemia-associated chromosome translocations has contributed relevant insights into our understanding of leukemia pathogenesis and has provided new specific tumor markers essential in prognostic assessment and minimal residual disease studies. The aim of this work is to study the frequency of AML1/ETO fusion gene in a series of Egyptian childhood AML cases. The clinical significance and prognostic implications of this aberration, including CR rate, duration of first CR, extramedullary leukemia (EML), and survival are investigated as well. Peripheral blood and/or bone marrow mononuclear cells were available for analysis from 78 children, all newly diagnosed with AML. AML1/ ETO fusion transcript was detected by the reverse transcriptase- polymerase chain reaction (RT-PCR) technique. Patients with de novo AML were treated by 2 courses of induction chemotherapy, followed by 4 courses of consolidation treatment if the patient achieved complete remission (CR). The marrow status was evaluated after each course in order to check bone marrow cellularity and presence of blasts. Patients with less than 5% blasts by the end of the second course of ADE passed to consolidation chemotherapy. Patients with more than 5% blasts by the end of the second course of ADE were excluded from the study. The AML1/ETO fusion transcript was detected by a singleround RT-PCR reaction and was found to be expressed in 15 out of 78 cases (19.2%). AML1/ETO positive patients were 7 girls and 8 boys, with ages ranging from 5 to 15 years. Seven cases (46.67%) belonged to FAB subtype M1, 7 (46.67%) M2, while only one case (6.67%) belonged to M5a subtype. Their total leukocytic counts ranged from 7.1 to 183.0 x 109/l with a median of 21.0 x 109/l. Their hemoglobin concentrations ranged from 4.8 to 10.3g/dl with a median of 7.4g/dl, while their platelet counts ranged from 6.0 to 96.0 x 109/l with a median of 25.5 x 109/l. Lymph nodes were enlarged in 8/15 cases (53.34%), hepatomegly was observed in 4/15 cases (26.67%), splenomegaly in 8/15 cases (53.34%), purpura in 6/15 cases (40%), while pallor was observed in all fifteen cases.Extramedullary leukemia occurred in 4/15 cases (26.67%). As regards the fate of the positive cases, thirteen cases (86.67%) attained complete remission (CR) following induction chemotherapy. Two patients (13.33%) died during induction in active disease. Eight patients were in complete continuous remission (CCR), four patients (26.67%) relapsed and died during relapse, and one patient (6.67%) died in complete remission due to severe neutropenia and infection. On comparing the AML1/ETO fusion gene status with overall survival, no significant difference was found between AML1/ETO positive and negative cases. Likewise, no difference could be found between positive and negative cases as regards disease-free survival (p=0.354). In conclusion, we report a frequency of 19.2% of AML1/ETO fusion gene in our newly diagnosed pediatric AML cases. Positive cases showed good response to induction therapy, as well as high complete remission rates, which are features of good prognosis. Key Words: Pediatric acute myeloid leukemia , AML1/ETO fusion gene , RT-PCR , Clinical outcome , Prognostic significance.
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PMID:AML1/ETO Fusion Gene in de novo Pediatric Acute Myeloid Leukemia: Clinical Significance and Prognostic Implications. 1883 34

A standardized, sensitive and universal method for minimal residual disease (MRD) detection in acute myeloid leukemia (AML) is still pending. Although hyperexpression of Wilms' tumor (WT1) gene transcript has been frequently proposed as an MRD marker in AML, wide comparability of the various methods used for evaluating WT1 expression has not been given. We established and standardized a multicenter approach for quantifying WT1 expression by quantitative reverse transcriptase PCR (qRT-PCR), on the basis of a primer/probe set combination at exons 6 and 7. In a series of quality-control rounds, we analyzed 69 childhood AML samples and 47 normal bone marrow (BM) samples from 4 participating centers. Differences in the individual WT1 expressions levels ranged within <0.5 log of the mean in 82% of the cases. In AML samples, the median WT1/1E+04 Abelson (ABL) expression was 3.5E+03 compared with that of 2.3E+01 in healthy BM samples. As 11.5% of childhood AML samples in this cohort harbored WT1 mutations in exon 7, the effect of mutations on WT1 expression has been investigated, showing that mutated cases expressed significantly higher WT1 levels than wild-type cases. Hence, our approach showed high reproducibility and applicability, even in patients with WT1 mutations; therefore, it can be widely used for the quantitation of WT1 expression in future clinical trials.
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PMID:Standardization of WT1 mRNA quantitation for minimal residual disease monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study. 1932 6


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