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)

Bcr-abl mRNA expression was studied in patients with chronic myeloproliferative disorders (CMPD) by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. A bcr-abl transcript was not found in any patient with polycythemia vera, essential thrombocythemia or primary myelofibrosis, suggesting that the bcr-abl rearranged clone is not present in CMPD other than chronic myelogenous leukemia (CML). In CML clinical and laboratory data were compared from three bcr-abl types: the bcr exon 2-abl exon 2 (B2-A2) type, bcr exon 3-abl exon 2 (B3-A2) type and the co-expression type. Age at diagnosis tended to be younger (p = 0.08) in the co-expression type, and the platelet count tended to be lower (p = 0.11) in the B2-A2 type. However, there was no difference in other data, including the duration of the chronic phase and the phenotype of blasts at blast crisis.
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PMID:Bcr-abl mRNA expression in patients with chronic myeloproliferative disorders--absence of bcr-abl fused clone except chronic myelocytic leukemia. 825

The bcr/abl fusion gene in 20 patients with chronic myeloid leukemia (CML) was detected by RNA polymerase chain reaction, which used mRNA as the starting material to generate cDNA with reverse transcriptase followed by PCR amplification (RNA/PCR). Amplification of a sequence spanning the bcr/abl junction region was achieved by using peripheral blood cells as the source of mRNA from all 20 patients with CML, including 3 cases of Ph (-) CML, and cell line K562 was derived from patients with CML. No amplification was seen when mononuclear cells from 3 normal individuals, 2 patients with lymphoma and cell line HL-60 were used. The presence or absence of bcr exon 3 in the fusion mRNA was determined by the size of the amplified fragments. Of the 20 CML patients, 15 showed only the 165-bp amplified band (indicating retention of bcr exon 3), one showed only the 90-bp amplified band, and 4 showed both 165-bp and 90-bp bands. Both bands were seen more frequently in blast crisis than in remission and chronic phase.
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PMID:Detection of the BCR/ABL fusion gene in chronic myeloid leukemia by RNA polymerase chain reaction. 829 58

It is now feasible to investigate bcr-abl transcription by the progeny of Ph-positive (Ph+) early and committed hemopoietic progenitor cells from patients with chronic myeloid leukemia (CML). Cells from individual colonies can be bisected and each half analyzed by cytogenetics or the reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect the bcr-abl transcript using internal nested oligonucleotide primers that flank the chimeric gene junction. We previously showed that some Ph+ colonies have undetectable PCR products for bcr-abl. When colonies are generated in the presence of alpha interferon (IFN-alpha) bcr-abl transcripts are undetectable in the majority of Ph+ colonies. These data suggest a potential mechanism for the action of IFN-alpha in Ph+ CML and indicate the need for a combined approach with cytogenetics and RT-PCR in analyzing the bcr-abl gene.
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PMID:Investigation of bcr-abl transcription by Ph-positive chronic myeloid leukemia progenitors. 829 75

We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.
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PMID:Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia. 835 Jun 22

We diagnosed a patient with chronic myelogenous leukemia (CML) in chronic phase (CP) on the basis of clinical findings, Ph1 chromosome detected by cytogenetic analysis, and bcr-abl fusion mRNA detected by reverse transcriptase-dependent polymerase chain reaction (RT-PCR). One month after diagnosis, the patient developed extramedullary blast crisis in the lymph nodes, and then medullary blast crisis in the bone marrow, in which different surface markers were shown. Combination chemotherapy with BH-AC, VP16, and mitoxantrone was administered; this resulted in rapid disappearance of the lymphadenopathy, restoration of normal hematopoiesis, and no Ph1 chromosome being detected by cytogenetic analysis. RT-PCR performed to detect the residual Ph1 clone revealed that although the Ph1 clone was preferentially suppressed, it was still residual. The intensive chemotherapy regimen preferentially suppressed the Ph1-positive clone and led to both clinical and cytogenetic remission in this patient with BC of CML; we suggest that RT-PCR is a sensitive and useful method for detecting minimal residual disease during the clinical course of this disease.
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PMID:Disappearance of Ph1 chromosome with intensive chemotherapy and detection of minimal residual disease by polymerase chain reaction in a patient with blast crisis of chronic myelogenous leukemia. 836 86

Interferon-alpha (IFN-alpha) is useful in the treatment of Philadelphia (Ph)-positive chronic myeloid leukaemia (CML). There is, however, a marked heterogeneity among CML patients in relation to their response to IFN-alpha treatment, the reasons for which are unknown. Since the reciprocal ABL-BCR gene is transcriptionally active in only a proportion of CML patients, it has been suggested that response to IFN-alpha may correlate with ABL-BCR expression. In the present study we have tested 209 Ph-positive CML patients for expression of ABL-BCR, BCR-ABL and the normal BCR and ABL genes by reverse transcriptase/polymerase chain reaction (RT/PCR). Whereas BCR-ABL, BCR and ABL transcripts were detected in all the patients, ABL-BCR expression was observed in 59% of the cases. A group of 105 patients within this series was treated with IFN-alpha; 33% achieved a complete or major cytogenetic response (< 35% Ph-positive metaphases) and the remaining 67% showed minimal or no response to IFN-alpha. The proportions of patients who were ABL-BCR positive (63%) and ABL-BCR negative (37%) were the same for good responders and poor responders, suggesting that there is no correlation between ABL-BCR expression and cytogenetic response to IFN-alpha in CML.
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PMID:Lack of correlation between ABL-BCR expression and response to interferon-alpha in chronic myeloid leukaemia. 861 36

In Philadelphia chromosome (Ph1) positive leukemias, the BCR gene is fused to the ABL gene. The resulting chimeric BCR-ABL oncoproteins are thought to play a central role in the pathogenesis of these diseases. We previously described two exons that can be spliced alternatively to the second BCR exon in place of the first exon to form minor messages. In this paper, we localize the alternative exons to a 4.1 kb BglII fragment in the 5' region of the large first intron of the BCR gene. This genomic structure is of interest because of its analogy to the organization of the ABL gene and because this part of the gene is not affected by the breakpoints occurring in Ph1-positive acute lymphoblastic leukemia (ALL). Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we detected the alternative messages in all cases of chronic myelogenous leukemia (CML) tested, including seven samples in the chronic phase, five in the accelerated phase and nine in the acute phase, as well as in the majority of other samples studied. These findings suggest a functional role for the variant transcripts.
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PMID:The first intron of the BCR gene contains two minor alternative exons. 863 66

The nested reverse transcriptase polymerase chain reaction (RT-PCR) provides a powerful tool for detection of minimal residual disease in CML. The RT-PCR used in the present study for detection of the major bcr-abl fusion gene, the hallmark and presumably the cause of CML, was optimized by: (a) increasing the amount of total RNA involved in the reverse transcription reaction to correspond to total RNA extracted from 10(8) cells; (b) using a specific abl primer in this reverse transcriptase reaction, and (c) reamplifying 10% of the RT-PCR product in a nested amplification. This optimized RT-PCR permitted to detect up to 1 copy of RNA bcr-abl synthesized in vitro, mixed with yeast RNA in a quantity equivalent to 10(8) white blood cells (WBC). Using the highly sensitive RT-PCR, a systematic study of the possible expression of bcr-abl RNA in WBC of healthy adults, children and umbilical cord blood (UCB) revealed the presence of bcr-abl transcripts in blood cells of 22/73 adults, 1/22 children but not in 22 samples of UCB. The comparison of these three groups indicated a significant tendency for the anomaly to increase in frequency with age.
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PMID:Very low level of major BCR-ABL expression in blood of some healthy individuals. 876 1

Neutrophilic-chronic myeloid leukemia (CML-N) is a rare myeloproliferative disorder that runs a much more benign course than chronic myeloid leukemia, and for which no specific underlying molecular lesion has been described so far. We have analyzed the genomic DNA by Southern blotting and the BCR/ABL hybrid gene transcripts by reverse transcriptase-polymerase chain reaction in three patients with clinical findings of CML-N, who did have a t(9;22) chromosomal translocation. In all patients we have found a rare type of BCR/ABL rearrangement, with a breakpoint between exons c3 and c4 of the BCR gene (corresponding to BCR exons 19 and 20). This was confirmed by hybridization with an oligonucleotide probe spanning the c3/a2 region. This type of junction causes almost the entire BCR gene to fuse with ABL. The junction is in frame and it gives rise to a fusion protein of predicted 230 kD. Our data now provide a molecular diagnostic marker for CML-N, and they are consistent with the notion that the inclusion or exclusion of BCR exons in the fusion protein affects dramatically its capacity to derange myeloid proliferation and differentiation, leading to the appearance of different disease phenotypes.
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PMID:Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction) 916 72

Chronic myelogenous leukemia is a disease of the pluripotent stem cell that involves the myeloid and, to a varying degree, the lymphoid compartment. We studied the involvement of B cells in chronic myelogenous leukemia at diagnosis and during treatment. B lymphocytes were immortalized by infection with Epstein-Barr virus. B-lymphoid cell lines could be established from 25 patients suffering from Philadelphia-chromosome (Ph1)-positive chronic myelogenous leukemia. The cell lines were tested for expression of the typical 210-kDa fusion protein, p210, using Western-blot analysis, and/or for mRNA expression of bcr-abl fusion genes, using reverse transcriptase polymerase chain reaction analysis. At diagnosis, mosaicism of B cells was demonstrated in every patient. During treatment with interferon alpha, p210-expressing B-lymphoid cell lines could not be established from 8 of 8 patients. Following discontinuation of IFN-alpha therapy, p210-positive cell lines were found early, even before cytogenetic recurrence. Resistance to IFN-alpha therapy and progression of the disease were both associated with the appearance of p210-positive cell lines. Cell lines established from 3 healthy individuals and from patients suffering from Ph1-negative diseases did not show p210 expression in Western blots. Our data suggest that B lymphocytes are involved early in the disease, and that B-cell mosaicism may be a sensitive marker for resistance to IFN-alpha therapy and disease progression.
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PMID:Mosaicicm in bcr-abl protein expression in B cells in chronic myelogenous leukemia. 893 37


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