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 treatment of chronic myelogenous leukemia(CML) is performed mainly by interferon (IFN) or/and allogeneic stem cell transplantation. Experimentally, some patients with CML are treated by autologous transplantation. Monitoring of minimal residual disease(MRD) in each patient is most important, regardless of the treatments. To detect MRD in CML patients, bcr-abl mRNA has been quantitated by competitive or real-time reverse transcriptase-polymerase chain reaction(RT-PCR) method. In patients who were treated by IFN, patients in whom the bcr-abl/abl ratio at the time of maximal response were lower than 0.045% were shown to have a significantly lower release rate. Allogeneic BMT patients, in whom the bcr-abl/abl ratio between 3 and 5 months after transplantation was less than 0.02% were recently found to have a significantly lower relapse rate at 3 year.
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PMID:[Minimal residual disease in chronic myelogenous leukemia]. 1176 37

Persistence of bcr-abl transcripts after marrow grafting is thought to convey a high risk for relapse in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Donor leukocyte infusion (DLI) is closely associated with development of graft-versus-host disease (GVHD) and has well-defined activity against relapsed chronic myelogenous leukemia (CML) but not ALL. We report two patients with Ph-positive ALL who remained bcr-abl positive by reverse transcriptase polymerase chain reaction (RT-PCR) after marrow grafting. Residual bcr-abl transcripts in both patients were eliminated following acute GVHD, which was induced by either DLI or rapid reduction of immunosuppression. Both patients have continued in complete molecular remission for 18 months and 8 months following transplantation, respectively. Our observation suggests that induction of GVHD may eliminate minimal residual disease, thereby preventing leukemia relapse in patients transplanted for Ph-positive ALL.
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PMID:Eradication of residual bcr-abl-positive clones by inducing graft-versus-host disease after allogeneic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. 1184 Jan 46

Chronic myelogenous leukemia (CML) with a minor bcr-abl transcript is a rare entity. We describe a 66-year-old female who was diagnosed with CML in the chronic phase. Molecular analysis of her Philadelphia chromosome using the reverse transcriptase polymerase chain reaction and subsequent sequencing revealed a minor bcr-abl transcript. Monocytosis resembling chronic myelomonocytic leukemia was observed without splenomegaly and basophilia. Her clinical course was indolent and maintained the chronic phase of CML for nearly 3 years under hydroxyurea treatment. A review of the 23 cases of m-bcr CML including this case showed the presence of monocytosis and the absence of basophilia and splenomegaly in 55.0%, 55.0%, and 70.0% of patients, respectively. The absence of basophilia was a significant finding in patients without monocytosis ( P=0.01). Although the hematological features or clinical outcomes were variable in m-bcr CML cases, all three cases at the onset of the blastic phase showed lymphoid crisis, implying an increased lymphoid leukemogenicity of minor bcr-abl transcripts.
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PMID:Lymphoid preponderance and the absence of basophilia and splenomegaly are frequent in m-bcr-positive chronic myelogenous leukemia. 1197 25

There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a p210 protein. Another fusion gene leads to the expression of an e1a2 transcript, which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2], which encodes a p230 protein. The incidence of one or the other rearrangement in chronic myeloid leukaemia (CML) patients varies in different reported series. This study was designed to determine the frequency of coexpresion of the p210, p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while the remaining 9.6% showed coexpression or one of the transcripts of p190/p210/p230. In 7% of patients with p210 expression there are both isoforms (b3a2/b2a2), presumably the result of alternative splicing. The rate of coexpression of the p190/p210 transcripts was 5%, which is much lower than in other reports. This may be due to the technical factors. These patients had high platelet counts, marked splenomegaly and chromosomal abnormalities in addition to Ph'. Other types of coexpression seen were p210/p230 and p190/p210/p230, in patients with high-risk clinical factors. Our study confirms the occurrence of coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much lower than has been reported in other populations. This may reflect either the sensitivity of the detection techniques used or the possibility of genetic differences between the populations studied. Coexpression may be due to alternative splicing or to phenotypic variation, with clinical courses different from classical CML.
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PMID:BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). 1206 77

The t(9;22) (q34;q11) between abl and bcr genes plays a pivotal role in the diagnosis and pathogenesis of chronic myelogenous leukemia(CML). To explore the bcr/abl fusion mRNA expression on hematopoietic precursors, reverse transcriptase-polymerase chain reaction(RT-PCR) was applied to detect bcr/abl mRNA expression on bone marrow cell colonies. Meanwhile, bcr/abl mRNA expressions on 14- or 28-day colonies using HPP-CFC and CFU-GM semisolid agar culture assay were also determined in 4 cases of confirmed Ph-positive CML by karyotyping analysis. The results showed that the bcr/abl mRNA expressions on 14-day colonies and some 14- or 28-day colonies detected singly were positive at presentation by RT-PCR, in agreement with results by karyotype analysis. Thus, a sensitive and powerful technique was offered for studying gene expression on hematopoietic precursors, diagnosis and therapeutic monitoring of CML. Furthermore, this can be used as an ideal method for revealing molecular mechanisms of pathogenesis of CML and screening anti-CML drugs.
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PMID:[Detection of bcr/abl gene expression on bone marrow cell colonies in chronic myelogenous leukemia by reverse transcriptase-polymerase chain reaction]. 1208 Jun 71

From 1994 to 2000, 154 adults with Philadelphia chromosome-positive (Ph(+)) and/or BCR-ABL(+) acute lymphoblastic leukemia (ALL) were treated according to a prospective trial (median follow-up, 4.5 years) with the aim to study the prognostic value of early response to therapy and the role of stem cell transplantation (SCT) in first complete remission (CR). All patients received a standard induction course followed by a course of mitoxantrone and intermediate-dose cytarabine (HAM). After each course, minimal residual disease was tested by specific reverse transcriptase-polymerase chain reaction (RT-PCR) (median sensitivity, 10(-5)). Allogeneic SCT (if a donor) or autologous SCT (if not) was planned at 3 months in all patients in CR after HAM. CR rates after induction, after HAM, and at 3 months were 53%, 67%, and 62%, respectively. High leukocyte count and m-bcr subtype were the 2 identified bad-prognosis factors for CR at 3 months, both superseded by a poor early response assessed at day 8 of the induction course. HAM-associated salvage rate was higher in patients with M-bcr than in those with m-bcr ALL (55% vs 30%; P =.05). In the 103 patients eligible for SCT, the existence of a donor and the negative BCR-ABL status after HAM were independently predictive of remission duration (P <.001 and.01, respectively) and survival (P =.02 and.01, respectively). Relapse was the most common cause of treatment failure in all patient groups. Allogeneic SCT in first CR is the current best treatment option in adults with the disease. New strategies must be tested during early phases of therapy to increase the rate of BCR-ABL(-) remissions.
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PMID:Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial. 1223 43

The WT1 gene encoding a zinc finger DNA-binding protein was identified as a tumor suppressor gene being responsible for Wilms' tumor. Recently, aberrant expression of WT1 gene and an inverse correlation between its expression levels and prognosis have been demonstrated in acute myeloid leukemia (AML), suggesting it is a novel tumor marker for leukemic blast cells. To explore whether the WT1 may be used as a marker for detection of minimal residual disease (MRD) in acute leukemia, we examined the sensitivity of the nested reverse transcriptase-polymerase chain reaction (RT-PCR) by using WT1 gene primers in comparison with tumor-specific marker genes, such as PML/RARalpha gene in NB4 cells or bcr-abl gene in K562 cells. In all samples, the integrity of RNA was confirmed by amplification of the c-abl gene as an internal control. The limits in amount of leukemic cells detected by two-step RT-PCR with primers for WT1 or tumor specific fusion gene were 10(-4) and 10(-5) in NB4 cells and 10(-3) to 10(-4) and higher than 10(-6) for K562 cells, respectively. None was WT1 positive in peripheral blood mononuclear cells (MNC) from 29 blood donors, while bone marrow MNCs from eight of 21 cases (38.1%) of nonmalignant patient WT1 gene expression were found. Our results suggested that monitoring of WT1 expression makes it possible to rapidly assess the effectiveness of treatment and follow up MRD in AML cases regardless of the presence or absence of tumor-specific markers.
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PMID:[Expression of the Wilms' Tumor Gene WT1 and Detection of Minimal Residual Disease in Acute Leukemia] 1257 85

We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase-polymerase chain reaction, fluorescence in situ hybridization (FISH), or both. Follow-up marrow biopsies, interphase FISH for bcr-abl, and conventional cytogenetics were performed at 3-month intervals (up to 24 months) after therapy initiation. All patients exhibited a reduction in bone marrow cellularity with decreases in myeloid/erythroid ratios at 3 to 6 months after therapy. The percentage of bcr-abl-positive cells by FISH decreased in all patients (pretherapy median, 73%; 3 months median, 47%). Cytogenetic and FISH data defined 2 groups after 6 months of follow-up: 5 patients became negative for bcr-abl by FISH; 8 remained positive, 4 of whom developed signs of clonal cytogenetic evolution. Patients who became negative for bcr-abl had no morphologic evidence of CML at 15 to 24 months of follow-up, whereas patients who remained positive redeveloped morphologic features of CML as cellularity increased. Some bcr-abl-positive patients showed signs of progression, including 2 patients who developed myeloid blast phase. Although all patients demonstrated an initial decrease in bone marrow cellularity after imatinib mesylate therapy, continued follow-up showed that histopathologic findings correlated with genetic response.
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PMID:Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status. 1281 31

Chronic myelogenous leukemia is characterized by the presence of the reciprocal t(9;22)(q34;q11) in which c-abl located on chromosome 9, and the bcr locus located on chromosome 22, are disrupted and translocated creating a novel bcr-abl fusion gene residing on the derivative chromosome 22. In most cases, the breakpoint in abl occurs within intron 1. Depending on the breakpoint in bcr, exon 2 of abl (a2) joins with exons 1 (e1), 13 (b2), or 14 (b3), or rarely to exon 19 (e19) of bcr resulting in chimeric proteins of p190, p210 and p230, respectively. Currently, several multiplex real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-based assays for detecting bcr-abl are available to assess the levels of the three common fusion transcripts, b2a2, b3a2 and e1a2. Although these assays circumvent the requirement for individual fusion sequence quantitative polymerase chain reaction-based assays, they do not identify the specific fusion transcript. Knowledge of the latter is useful to rule out false-positive results and to compare clones before and after therapy. We designed a novel multiplex real-time RT-PCR assay to detect bcr-abl that allows accurate quantification and determination of the specific fusion transcript. In this assay, abl primer labeled at its 5' end with the fluorescent dye NED (Applied Biosystems) is incorporated into the bcr-abl fusion product during amplification. The NED fluorescent dye in abl primer, without interfering with fluorescent TaqMan probe signal, allows subsequent identification of the fusion transcript by semiautomated high-resolution capillary electrophoresis and GeneScan analysis.
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PMID:TaqMan RT-PCR assay coupled with capillary electrophoresis for quantification and identification of bcr-abl transcript type. 1465 55

We previously showed that Wilms tumor gene (WT1) expression level, measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), was useful as an indicator of minimal residual disease (MRD) in leukemia and myelodysplastic syndrome. However, in conventional quantitative RT-PCR (CQ-PCR), RT-PCR must be performed for various numbers of cycles depending on WT1 expression level. In the present study, we developed a new real-time quantitative RT-PCR (RQ-PCR) method for quantitating WT1 transcripts. Results of intraassay and interassay variability tests demonstrated that the real-time WT1 assay had high reproducibility. WT1 expression levels measured by the RQ- and the CQ-PCR methods were strongly correlated (r = 0.998). Furthermore, a strong correlation was observed among WT1 transcript values normalized with 3 different control genes (beta-actin, ABL, and glyceraldehyde-3-phosphate dehydrogenase) and between relative WT1 transcript values with WT1 expression in K562 cells as the reference and absolute WT1 transcript copy numbers per microgram RNA. When WT1 expression and minor bcr-abl expression were concurrently monitored in 2 patients with bcr-abl-positive acute lymphoblastic leukemia, both MRDs changed mostly in parallel, indicating the reliability and validity of our RQ-PCR method. In conclusion, this RQ-PCR method is convenient and reliable for monitoring MRD and enables routine clinical use of a WT1 assay.
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PMID:Monitoring minimal residual disease in leukemia using real-time quantitative polymerase chain reaction for Wilms tumor gene (WT1). 1468 94


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