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)

Molecular techniques to detect MLL (11q23) and AF-4 (4q21) gene rearrangements are being evaluated for use in stratification of patients into prognostic groups. We studied 15 cases of infant acute lymphoblastic leukemia (ALL) with Southern blotting for MLL gene rearrangement and reverse transcriptase-polymerase chain reaction (RT-PCR) for t(4;11) fusion transcripts and compared the results to cytogenetic and clinical data. Our results indicate that classic t(4;11)(q21;q23) translocations are detected by RT-PCR; however, unusual 4;11 translocations still require additional investigation. We also extended and updated our original study of MLL gene rearrangement in infant ALL to 40 patients with longer follow-up and show that the group with germline configuration of the MLL gene continues to have an excellent outcome. The results of salvage therapy (bone marrow transplantation or chemotherapy) suggest that transplant may show advantage. Preliminary results of the use of RT-PCR to assess minimal disease are also reported.
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PMID:Molecular analysis of infant acute lymphoblastic leukemia: MLL gene rearrangement and reverse transcriptase-polymerase chain reaction for t(4; 11)(q21; q23). 757 56

In this paper we describe a patient with bcr/abl positive acute undifferentiated leukemia (AUL) derived from acquired sideroblastic anemia secondary to ifosphamide treatment given for the preceding non-Hodgkin lymphoma of the lung. Cytogenetically, Philadelphia chromosome was not detected through the whole course in this patient, and multiple chromosomal abnormalities including 5q- and monosomy 7 were found at the stage of sideroblastic anemia. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed no bcr/abl fusion transcript at the diagnosis of malignant lymphoma. The mRNA encoding the major bcr/abl fusion protein then appeared in the stage of sideroblastic anemia. Finally, the mRNA encoding both major and minor bcr/abl was detected in the stage of AUL transformation. MLL gene rearrangement was not found by RT-PCR analysis at any stage of the disorder. These results may be direct evidence for the induction of the bcr/abl fusion gene by treatment with an alkylating agent (ifosphamide).
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PMID:Detection of major and minor bcr/abl fusion gene transcripts in a patient with acute undifferentiated leukemia secondary to treatment with an alkylating agent. 759 51

Various kinds of nonrandom chromosomal aberrations have been reported in hematopoietic malignancies. Since the 1980s, many translocation-associated oncogenes and several suppressor oncogenes have been identified and applied for the clinical diagnosis of these malignancies. The former is of major, clinical importance for specific diagnosis made on the basis of molecular detection of the chromosomal translocation, the deregulated expression, and the chimeric mRNA of those genes. Both BCL-1 and BCL-2 genes, associated with mantle zone lymphoma and follicular lymphoma, respectively, belong to the representative deregulated oncogenes by juxtaposition with an immunoglobulin gene enhancer as well as an MYC gene in Burkitt's lymphoma. On the other hand, the MLL gene, associated with infant leukemia, acute monocytic leukemia and secondary leukemia, produces chimeric mRNAs between LTG4, 9, and 19 genes as well as the BCR-ABL chimeric gene in chronic myelogenous leukemia. The detection of minimal residual disease (MRD) by either polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR is becoming an essential test during the course of treatment containing bone marrow transplantation, because positive results of the MRD are closely related to poor prognosis and would have great influence on the choice of treatment plans.
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PMID:[Molecular diagnosis of leukemia and lymphoma]. 817 45

The MLL gene involved in 11q23 translocations found in the majority of infantile leukemias and some secondary leukemias makes fusion transcripts with genes such as LTG4 (chromosome 4), LTG9 (chromosome 9), and LTG19 (chromosome 19) as a result of reciprocal translocation. We have examined 25 cases of leukemias with 11q23 abnormalities by Southern blot analysis and the reverse transcriptase-polymerase chain reaction (RT-PCR). Using various primer pairs, chimeric mRNAs could be amplified in 6 of 7 leukemias with t(4;11), 6 of 8 leukemias with t(9;11) including secondary leukemia, 8 of 9 leukemias with t(11;19), and 1 with a deletion at 11q23. The chimeric mRNAs were heterogeneous and differential usage of the MLL exons was found, irrespective of the partner chromosomes. Sensitivity studies showed that a single clone with chimeric mRNA in 10(4) to 10(5) cells could be detected. These findings show that the present RT-PCR settings provide a rapid, accurate, and sensitive tool for diagnosing leukemias with 11q23 translocations and for monitoring response to therapy in these patients.
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PMID:A reverse transcriptase-polymerase chain reaction detects heterogeneous chimeric mRNAs in leukemias with 11q23 abnormalities. 818 Mar 86

We have designed a single polymerase chain reaction (PCR) primer pair that detects the MLL/AF-4 fusion mRNA encoded by the derivative 11 chromosome from t(4;11)(q21;q23) leukemia cells using the reverse transcriptase PCR technique. PCR amplification was possible in seven of seven cells studied. Sequencing of the amplified products showed three different breakpoints on 11q23 and three on 4q21, resulting in six unique fusion sequences. All fusion sequences maintained an open reading frame. The areas of the MLL and AF-4 genes that are conserved in all derivative 11 fusion RNAs and therefore likely to contribute to the function of the oncogenic fusion protein are centromeric regions of MLL through exon 6 (retaining the AT hook motif) and telomeric regions of AF-4 beginning at codon 491 (containing nuclear localization and GTP-binding motifs). A single primer pair was able to detect the derivative 11 fusion transcript in seven of seven cases of t(4;11) acute leukemia tested. Given the variability shown in specific fusion sequences, studies correlating differential exon usage with clinical parameters will require different fusion-specific oligonucleotides or PCR primer pairs.
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PMID:Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia. 835 9

Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic abnormality seen in acute monocytic leukemia. We also isolated a normal MLLT3 cDNA and found an open reading frame encoding at least 318 amino acids with high serine/proline content (24.8%). The chimeric mRNAs were demonstrated to be fused to MLL in frame, as found in t(11;19) and t(4;11) leukemias. The predicted MLLT3 protein demonstrated a significant homology to that of the MLLT1 gene at 19p13 involved in t(11;19) leukemia. The highest homology, up to 74.1%, was found in 86 amino acids of the C-terminus, suggesting that this region is of particular importance for leukemogenesis in t(9;11) leukemia. Northern blot analysis with the MLLT3 cDNA probe against normal tissues revealed multiple transcripts in lymphoid organs. A survey of hematopoietic cell lines demonstrated relatively stronger signals in cells belonging to megakaryocytic and erythroid lineages. As previously found in t(11;19) leukemia, heterogeneous MLL-MLLT3 chimeric mRNAs could be detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) in t(9;11) leukemia samples.
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PMID:MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13. 841 10

MLL (also known as ALL-I, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, MLL gene rearrangements are uncommon in T-cell ALL. We recently detected an MLL gene rearrangement in a patient with typical T-cell ALL. We recently detected an MLL gene rearrangement in a patient with typical T-cell ALL (CD2+, CD4+, CD5+, CD7+, CD8+, HLA DR-) and an apparently normal karyotype (46,XX). The rearrangement was cloned and characterized; a DNA fragment distal to the breakpoint was mapped by fluorescence in situ hybridization (FISH) to 19p13, indicating that the leukemic blasts had undergone a cytogenetically undetected rearrangement involving chromosomes 11 and 19. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated an in-frame fusion mRNA between the amino terminus of MLL and the carboxy terminus of ENL (also known as MLLT1 or LTG19), a gene that has been mapped to 19p13. In addition, MLL sequences distal (telomeric) to the breakpoint were deleted from the genome, which precludes the formation of a reciprocal ENL/MLL fusion protein. These findings suggest that an MLL/ENL fusion protein (and not a reciprocal ENL/MLL fusion) was likely to be pathogenic in this patient, and they reinforce previous studies showing that leukemic blasts with apparently normal karyotype may harbor MLL rearrangements. Additionally, this report provides the first conclusive evidence of an MLL/ENL gene fusion characterized at a molecular level in a patient with T-cell ALL.
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PMID:Complex MLL rearrangement in a patient with T-cell acute lymphoblastic leukemia. 852 89

MLL is fused to ENL or ELL in acute leukemias that contain t(ll;19)(q23;p13). Although ENL and ELL localize to chromosome 19, bands p13.3 and p13.1, respectively, these breakpoints are not always readily distinguished by standard cytogenetics. We therefore used reverse transcriptase-polymerase chain reaction (RT-PCR) assays to analyze 26 cases of childhood acute leukemia containing t(11;19) to determine the frequencies of ENL and ELL involvement. All 17 cases of acute lymphoblastic leukemia (ALL) had MLL/ENL fusion transcripts. By contrast, of the 9 cases of acute myeloid leukemia (AML) analyzed, 6 had MLL/ENL fusions, 2 had MLL/ELL fusions, and 1 case had no RT-PCR-detectable MLL fusion mRNA. These data suggest that the majority of 11;19 translocations involve ENL, whereas involvement of ELL is relatively uncommon in childhood acute leukemia and may be restricted to AML.
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PMID:Molecular analysis of t(11;19) breakpoints in childhood acute leukemias. 863 52

Rearrangement of the MLL (myeloid-lymphoid or mixed-lineage leukemia) gene through a reciprocal chromosomal translocation is found in 5% of adult acute myeloid (AML) and 10% of pediatric acute lymphoid (ALL) leukemia. More than 25 different reciprocal chromosomal translocations, with an 11q23 breakpoint, fuse the MLL gene (also named ALL-1, HRX and Htrx1) to a second partner gene. These leukemias have poor prognosis and frequently have a monocytic, lymphoid or biphenotypic (myeloid and lymphoid) antigen expression in blast cells. Approximately 20-30% of patients diagnosed as having adult de novo, AML have normal chromosomes by metaphase analysis and the majority of these patients have good prognosis. With the use of reverse transcriptase-polymerase chain reaction (RT-PCR) technique and Southern blot analysis, we found that seven of 34 such patients (21%) had a tandem partial duplication of exons 2 to 6 or 2 to 8 of the MLL gene. These seven patients showed a median survival of 2.7 months, compared to a 6.8 months median survival for all other patients in the study. If confirmed on a large series of patients, our findings may help differentiate AML with normal karyotype and poor prognosis from those with normal karyotype and a more favorable prognosis.
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PMID:MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype. 865 71

Recurrent translocations involving chromosome band 11q23 are often found in human acute leukemias. Recently, the MLL gene on 11q23 and 10 partner genes involved in these translocations have been cloned and characterized. We performed a reverse transcriptase-polymerase chain reaction (RT-PCR) to detect the resultant der(11) chimeric mRNAs of the 3 types of 11q23 translocations including t(4;11), t(9;11), or t(11;19), in 14 leukemia patients with MLL gene rearrangements. At diagnosis or relapse, chimeric mRNA could be detected in all of the 4 patients with t(4;11), 2 of 3 with t(9;11), 2 of 3 with t(11;19), and 1 of 4 with unsuccessful karyotype. In 5 patients, we could monitor minimal residual disease (MRD) serially through the clinical course. One patient, in whom chi-meric mRNA was detected during complete remission (CR) just after the induction chemotherapy, relapsed within 2 months and died, while 2 patients in which chimeric mRNA was not detected remained in CR from 10-23 months. These findings suggest that RT-PCR is a useful approach for detecting which partner gene is involved in the translocation and monitoring MRD in patients with MLL gene rearrangement. Nonetheless, the clinical relevance of MRD evaluation by RT-PCR monitoring remains controversial. Long-term and prospective investigation of a larger series of patients is needed to confirm the clinical significance of monitoring MRD by RT-PCR method.
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PMID:Detection of chimeric mRNAs by reverse transcriptase-polymerase chain reaction for diagnosis and monitoring of acute leukemias with 11q23 abnormalities. 954 32


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