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)

Approximately 2-5% of children with newly diagnosed acute lymphoblastic leukemia (ALL) have a Philadelphia (Ph) chromosome detectable on cytogenetic analysis, which is associated with a poor prognosis. In rare ALL cases the Ph chromosome may appear in leukemic cells during the course of the disease. We report here the case of a 5.5-year-old male patient with T-ALL who was found to have the b2a2 BCR-ABL mRNA transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) at first marrow relapse. At the time of initial diagnosis, no BCR-ABL transcripts had been detected by PCR in the patient's blood and marrow samples. Further studies were performed using a competitive PCR titration assay and the fluorescence in situ hybridization (FISH) method to monitor the leukemic clone. Progression of the disease was associated with a higher BCR-ABL transcript level and an increasing proportion of BCR-ABL-positive cells. Metaphase FISH analysis identified the presence of the BCR-ABL fusion gene on a normal chromosome 22. This study shows that a late-appearing Ph translocation in ALL may be cytogenetically invisible. Quantitative RT-PCR and FISH techniques are appropriate and efficient methods for detecting these rare ALL variants expressing the BCR-ABL fusion gene and for estimating the level of residual disease following treatment.
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PMID:Molecular detection of a late-appearing BCR-ABL gene in a child with T-cell acute lymphoblastic leukemia. 976 Jan 54

Detection of residual disease after completion of therapy or following bone marrow transplantation (BMT) in patients with acute promyelocytic leukaemia (APL) predicts relapse and is associated with a poor prognosis. Here we describe the successful treatment of residual disease post-transplant in APL using prolonged all-trans retinoic acid (ATRA) therapy in two children in whom autologous BMT (ABMT) had been performed in second complete remission (CR). ATRA treatment was well tolerated and found to be beneficial despite its prior use as a component of the initial induction protocol. ATRA therapy post-transplant led to molecular remission as determined by fluorescence in situ hybridization (FISH) as well as reverse transcriptase-polymerase chain reaction (RT-PCR) analyses and remission now exceeds 3.5 years in both patients. Overall, this study not only demonstrates that ATRA may successfully salvage APL patients with residual disease post-transplant, but also suggests a potential role for retinoids post-consolidation as a means of eliminating residual disease which could be beneficial even in patients previously exposed to ATRA as a component of the induction protocol.
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PMID:Salvage of patients with acute promyelocytic leukaemia with residual disease following ABMT performed in second CR using all-trans retinoic acid. 982 35

Molecular dissection of physiologic and pathologic genetic phenomena in hematologic malignancy has provided the pathologist with a broad menu of new assays. By integrating the data gleaned from these techniques we can formulate more rational and biologically based diagnoses, which should lead to the ultimate goal of targeted therapy for these specific entities. We summarize some of the more relevant molecular genetic assays and present an overview of those genetic mechanisms usually evaluated in the current practice of hematopathology. The usefulness of such assays extends beyond refining diagnoses in that they also provide relevant prognostic information. Moreover, since most are based on the polymerase chain reaction and reverse transcriptase polymerase chain reaction, we are more sensitively able to monitor for residual disease after attempts at curative therapy, and our definition of remission has been dramatically altered. However, molecular genetic tests are not without limitations, and we must remain cognizant of their cost effectiveness and be aware of current deficiencies in standardization. The challenge will be to meaningfully and economically harness and integrate the information we obtain from these and future technologies into appropriate clinical practice.
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PMID:Molecular pathology of leukemia and lymphoma. 1039 3

A substantial minority of patients with chronic myelogenous leukemia (CML) achieve a complete response (CR) to treatment with interferon-alpha (IFN), defined as the disappearance of Philadelphia chromosome-positive metaphases. Currently it is unclear how long IFN treatment should be continued for such patients. We used a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify levels of BCR-ABL transcripts in 297 peripheral blood specimens collected from 54 patients who had achieved CR with IFN. The median duration of observation was 1.9 years (range, 0.3-11.0 years). Total ABL transcripts were quantified as internal control and results were expressed as the ratio BCR-ABL/ABL. All 54 patients had molecular evidence of residual disease, although 3 patients were intermittently PCR negative. The median BCR-ABL/ABL ratio at the time of maximal response for each patient was 0.045% (range, 0%-3. 6%). During the period of observation 14 patients relapsed, 11 cytogenetically to chronic phase disease and 3 directly to blastic phase. The median ratio of BCR-ABL/ABL at maximal response was significantly higher in patients who relapsed than in those who remained in CR (0.49% versus 0.021%, P < 0.0001). Our findings show that the level of residual disease falls with time in complete responders to IFN, but molecular evidence of disease is rarely if ever eliminated. The actual level of minimal residual disease correlates with the probability of relapse. We suggest that for patients who reach CR, IFN should be continued at least until relatively low levels of residual leukemia are achieved. (Blood. 2000;95:62-66)
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PMID:Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. German CML Study Group and the UK MRC CML Study Group. 1060 85

Improvement is needed in the ability to evaluate the prognosis of melanoma patients who are clinically disease-free but likely to develop recurrent metastatic disease. The detection of circulating melanoma cells in blood is a potential surrogate marker of subclinical residual disease. We assessed the prognostic clinical utility of a multimarker melanoma reverse transcriptase-PCR (RT-PCR) assay using blood of 46 patients who were clinically disease-free. All patients were followed up for more than 4 years for disease recurrence. There was a significant correlation between number of RT-PCR markers present in blood and American Joint Committee on Cancer stage (P = 0.009). The number of RT-PCR markers detected in blood was an independent prediction factor of disease recurrence in a Cox proportional hazard model (P = 0.02). A risk factor model using American Joint Committee on Cancer stage and number of positive RT-PCR markers significantly predicted disease recurrence in 2, 3, and 4 years of follow-up. These studies demonstrate that molecular detection of circulating melanoma cells may be of significant prognostic value in determining early disease recurrence and may be useful for stratifying patients for adjuvant therapy.
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PMID:Molecular markers in blood as surrogate prognostic indicators of melanoma recurrence. 1078 92

Wilms' tumor gene WT1 mRNA is a new marker of leukemic blast cells for AML, ALL, and CML. Minimal residual disease(MRD) of leukemia can be detected at frequencies as low as 1 in 10(3) to 10(4) normal bone marrow cells and 1 in 10(5) normal peripheral blood mononuclear cells by means of the quantitation of WT1 mRNA(WT1 assay) using reverse transcriptase-polymerase chain reaction. Thus, the WT1 assay makes it possible to rapidly assess the effectiveness of treatment and to evaluate the degree of eradication of leukemic cell in individual leukemia patients. Furthermore, WT1 assay can continuously assess the disease progression of myelodysplastic syndromes(MDS) and predict the evolution of MDS to overt AML within 6 months.
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PMID:[Genetic diagnosis of leukemia: diagnosis of relapse and complete remission, and prediction of leukemia onset]. 1080 19

Despite recent progress in early detection and local curative therapy, patients with primary epithelial cancer quite frequently relapse with incurable metastasis. Early disseminated tumor cells that may be seminal for distant failure and are undetectable by current diagnostic methods have been identified by immunocytochemical techniques in bone marrow of cancer patients using monoclonal antibodies against cytokeratins. Recently, promising new molecular approaches, namely, reverse transcriptase--polymerase chain reaction (RT-PCR) assays, have been suggested as a potential technique for the detection of minimal residual tumor burden by targeting mRNA transcribed from epithelial genes in bone marrow, peripheral blood, or lymph nodes. Several studies using RT-PCR thus far indicate a highly sensitive and specific staging tool, although the prognostic value is still controversial. However, limitations may arise from ectopic expression of marker mRNA in hematopoietic cells and deficient expression in circulating tumor cells. The present review focuses on the relevant literature and demonstrates the range of current applications of RT-PCR-based assays for detecting disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. We will both summarize technical evaluations of published molecular approaches and discuss the widely disparate results on PCR findings in clinical studies.
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PMID:RT-PCR-based detection of occult disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. An overview. 1081 6

A 15-year-old girl with Ph-positive chronic myelogenous leukemia in first chronic phase received bone marrow from her human leukocyte antigen matched brother. Twenty three months after bone marrow transplantation hematological relapse occured which was treated with two infusions of donor lymphocytes (DLI) (0.5x10(8) CD3/kg b.w./infusion). To enforce the graft-versus-leukemia effect (GvL), the first DLI was followed by administration of interferon-alpha (INF-alpha) 6x10(6) U/day for 30 days, whereas, after the second infusion INF-alpha was given at the same dose until hematological remission was achieved (80 doses). Minimal residual disease (MRD) was detected by conventional cytogenetics (Ph chromosome), fluorescence in situ hybridization (FISH) cytogenetics (BCR/ABL translocation) and reverse transcriptase-polymerase chain reaction (RT-PCR) Ecotropic virus integration site-1 (EVI-1 gene expression), whereas cellular chimerism was monitored by assessment of microsatellite markers PCR and Y-chromosomal DNA content FISH. When hematological remission was achieved the pancytopenia was observed and the cytogenetic and molecular investigations revealed only partial remission and mixed chimerism, however, with predominance of donor origin hematopoiesis. To diminish the myelosupressive effect of donor CD3 cells without switching-off the GvL effect, a low dose of cyclosporine A was given. Further observation revealed significant improvement of hematopoiesis with parallel gradual decline of MRD and increase of donor hematopoiesis up to complete chimerism. Graft-versus-host disease was not observed at any stage of the treatment.
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PMID:Donor lymphocyte infusion followed by interferon-alpha plus low dose cyclosporine A for modulation of donor CD3 cells activity with monitoring of minimal residual disease and cellular chimerism in a patient with first hematologic relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. 1124 34

Detection of breast cancer micrometastases based on specific genetic markers may provide useful information to justify appropriate therapeutic strategies. We examined the presence of a carcinoembryonic antigen (CEA) messenger RNA(mRNA) in the peripheral blood of 32 patients with varying stages of breast cancers by means of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay prior to and after the curative operation. CEA mRNA were detected in the peripheral blood samples from 12 (38%) out of 32 breast cancer patients prior to surgery. Among 12 CEA mRNA-positive patients prior to surgery, 4 (33.3%) relapsed from breast cancer within 2 years after surgery. Moreover, CEA mRNA was detected in the peripheral blood samples obtained prior to surgery in 3 out of 11 patients (27.2%) with a stage I disease. One out of three of these patients had a relapse in lung. There were four patterns of CEA mRNA expression, ( +, + ), (+, -), (-, + ), and (-, -) in the pre- and post-operative blood samples. In 12 CEA mRNA-positive patients submitted to surgical resection of the primary tumor, persistence of CEA mRNA expression was observed in five patients (+, +) within a month after surgical treatment. Three out of these 5 patients (60%) relapsed from breast cancer within 2 years after surgery. In 7 other patients (+, -), CEA mRNA expression was not detected within a month after tumor removal, and recurrence occurred in 1 out of the 7 patients (14%) within 2 years after surgery. In 19 patients, CEA mRNA expression was not detected in pre- or post-operative blood samples (-, -). There was a patient whose blood sample was negative for CEA mRNA before the operation, but changed to show a positive result after surgery (-,+). No recurrence was found in 20 of CEA mRNA-negative patients prior to surgery (-, +), (-, -). This study suggested that the presence of CEA mRNA expression in preoperative peripheral blood sample represent the progression of the disease, especially the risk of hematogenous metastasis in the patients in spite of their clinical stage, and the presence of CEA mRNA in the postoperative blood sample may represent the evidence of a residual disease. Thus consideration might be given for adding combined multi-modal therapy.
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PMID:Clinical significance of circulating cancer cells in peripheral blood detected by reverse transcriptase-polymerase chain reaction in patients with breast cancer. 1131 30

Acute promyelocytic leukemia (AML M3) is a well-defined subtype of leukemia with specific and peculiar characteristics. Immediate identification of t(15;17) or the PML/RARA gene rearrangement is fundamental for treatment. The objective of the present study was to compare fluorescent in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and karyotyping in 18 samples (12 at diagnosis and 6 after treatment) from 13 AML M3 patients. Bone marrow samples were submitted to karyotype G-banding, FISH and RT-PCR. At diagnosis, cytogenetics was successful in 10 of 12 samples, 8 with t(15;17) and 2 without. FISH was positive in 11/12 cases (one had no cells for analysis) and positivity varied from 25 to 93% (mean: 56%). RT-PCR was done in 6/12 cases and all were positive. Four of 8 patients with t(15;17) presented positive RT-PCR as well as 2 without metaphases. The lack of RT-PCR results in the other samples was due to poor quality RNA. When the three tests were compared at diagnosis, karyotyping presented the translocation in 80% of the tested samples while FISH and RT-PCR showed the PML/RARA rearrangement in 100% of them. Of 6 samples evaluated after treatment, 3 showed a normal karyotype, 1 persistence of an abnormal clone and 2 no metaphases. FISH was negative in 4 samples studied and 2 had no material for analysis. RT-PCR was positive in 4 (2 of which showed negative FISH, indicating residual disease) and negative in 2. When the three tests were compared after treatment, they showed concordance in 2 of 6 samples or, when there were not enough cells for all tests, concordance between karyotype and RT-PCR in one. At remission, RT-PCR was the most sensitive test in detecting residual disease, as expected (positive in 4/6 samples). An incidence of about 40% of 5' breaks and 60% of 3' breaks, i.e., bcr3 and bcr1/bcr2, respectively, was observed.
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PMID:Acute promyelocytic leukemia: the study of t(15;17) translocation by fluorescent in situ hybridization, reverse transcriptase-polymerase chain reaction and cytogenetic techniques. 1137 61


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