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)

Imatinib induces a high complete cytogenetic response (CCR) rate in relapsed chronic myelogenous leukemia. By analyzing minimal residual disease (MRD) under the levels of CCR, we tried to assess the molecular response after imatinib therapy. By using real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR), MRD was evaluated in 23 patients (3 in cytogenetic relapse, 6 in chronic phase, 9 in accelerated phase, and 5 in blast crisis) who were treated with standard-dose imatinib for relapsed chronic myelogenous leukemia after allogeneic stem cell transplantation. With a median therapy time of 399 days (range, 35-817 days), 19 (83%) patients achieved a CCR. Meanwhile, 11 (58%) of them achieved a molecular remission (MR), which was associated with improved survival. The Q-RT-PCR data were compared according to the best response (MR, n = 11; CCR, n = 8) in the patients achieving a CCR. The BCR-ABL/ABL ratios were similar in 2 groups at 3 months but were significantly different at 6 months (median, 0.0000012 for MR and 0.00022 for CCR; P =.003). The probability of a subsequent MR was significantly higher in patients with a lower BCR-ABL/ABL ratio at 6 months (100% for <0.0001 versus 33% for >/=0.0001; P =.006) or a greater reduction in the level between 3 and 6 months (log-reduction >/=1.0;, 100%; <1.0, 17%; P =.003). Q-RT-PCR is a reliable method for monitoring MRD: the early trends in the BCR-ABL/ABL ratio may be clinically useful in discriminating patients who will achieve an MR from those who will remain in CCR.
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PMID:Early prediction of molecular remission by monitoring BCR-ABL transcript levels in patients achieving a complete cytogenetic response after imatinib therapy for posttransplantation chronic myelogenous leukemia relapse. 1538 38

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Chronic Myeloid Leukaemia (CML) is a good example to investigate the reactivation of telomerase as; after a variable period in chronic phase, CML undergoes further evolution. The aim of this work is to study telomerase activity in patients with philadelphia- positive CML and to compare the relative amount of telomerase activity between chronic phase, accelerated phase and blastic crisis. The study is conducted on 3 groups. Group I comprised ten newly diagnosed CML patients in chronic phase; five males and five females their ages ranged from 24-63 years (X = 44.1 +/- 11.2 years). Group II comprised ten patients in acute transformation (accelerated or blastic crisis phase); seven were males and three were females their ages ranged from 14 to 63 years ( X = 35.7 +/- 16.2 years). Ten healthy subjects comprised the control group III; five males and five females their ages ranged from 14-50 years ( X = 31.8 +/- 12.4 years). All patients were subjected to thorough history taking and clinical examination, complete blood picture with differential cell counts, bone marrow aspiration and/or biopsy, neutrophil alkaline phosphatase scoring by cytochemistry, immunophenotyping to identify the type of blast crisis, chromosomal analysis to detect Ph-positive cases, and measurement of telomerase activity by PCR-ELISA technique. Telomerase activity was highest in acute transformation with a range of (0.252-1.896) and mean of 1.521 0.496, while in chronic phase ranged between 0.67 and 0.743 with a mean of 0.305 +/- 0.109 and in normal controls the range was 0.45 to 0.195 with a mean of 0.102 +/- 0.048. The difference between groups was statistically significant. No correlation was found between the activity of the telomerase and hemoglobin, platelet, leucocyte counts, percentage of peripheral blood, bone marrow blasts, basophils, bone marrow cellularity, the type of crisis as well as leucocyte alkaline phosphatase scoring. In conclusion; The increased level of telomerase activity as noticed in the different stages of CML indicates its association with disease progression and can be used as a useful marker for evaluating development of the course.
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PMID:Telomerase activity in Philadelphia positive chronic myeloid leukaemia. 1572 80

Expression of the CDH13 gene in chronic myeloid leukaemia (CML) patients at different clinical stages, and its relationship with the BCR/ABL fusion gene, is investigated. Expression of the CDH13 gene and the BCR/ABL fuse gene is investigated in peripheral blood from 30 healthy adults, 25 primary CML patients and 25 CML patients in blast crisis using the EvaGreen real-time reverse transcriptase polymerase chain reaction (RT-PCR). Results showed that BCR/ABL fusion gene expression in the blast crisis CML patients was 4.72-fold higher than that in patients with primary CML. Expression of CDH13 mRNA in primary and blast crisis CML patients was lower than in the healthy adults, reduced 64% and 75%, respectively. Expression of CDH13 showed a negative correlation with the BCR/ABL fusion gene. The data indicate that the decline of CDH13 expression accompanied the different clinical stages of CML and probably was involved in over-expression of the BCR/ABL fusion gene.
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PMID:Cadherin-13 in primary and blast crisis chronic myeloid leukaemia: declining expression and negative correlation with the BCR/ABL fusion gene. 1934 22

Chronic myeloid leukemia (CML) is a neoplastic disease of the hematopoietic stem cell. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) may up-regulate the transcriptional activity of some oncogenes in cancerous cells. The aim of this study was to verify the expression pattern of hnRNPK in patients with CML, to explore its association with BCR-ABL and some abnormal signaling pathways, and to discover how hnRNPK contributes to the progression of CML. In this study, 15 patients with CML (9 in chronic phase and 6 in blast crisis) were enrolled in this study. The expression of hnRNPK in mononuclear cells (MNCs) from these patients was detected by Western blotting and fluorimeter-based quantitative real-time reverse transcriptase polymerase chain reaction. hnRNPK expression levels in K562 cell line and imatinib-resistant leukemic cell line K562R, following the treatments with the inhibitors of Ras-MAPK (PD98059), PI3K/AKT (LY294002), JAK/STAT (AG490) signaling pathways, and BCR-ABL [imatinib mesylate (IM)], were also determined. As the results, the overexpression of hnRNPK in protein and gene patterns was detected in MNCs from patients with CML comparing with normal donors. Especially, its level in MNCs from patients with CML-blast crisis was significantly higher than in CML-chronic phase cells (P < 0.01). After the treatment with PD98059 (at 4, 8, 24, and 48 h) and IM (at 48 h), the expression levels of hnRNPK in leukemic cell lines were decreased, comparing with DMSO control group (P < 0.05). In conclusion, the results suggest that the overexpression of hnRNPK, which is regulated by BCR-ABL and Ras-MAPK signaling pathways, may promote the progression of CML. hnRNPK would be a potential marker and therapeutic target of CML evolution.
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PMID:The role of heterogeneous nuclear ribonucleoprotein K in the progression of chronic myeloid leukemia. 1965 39

This study was purposed to investigate the expression of the growth-factor independence 1 (GFI1) in patients with leukemia and its clinical significance. Bone marrow mononuclear cells were obtained from 65 newly diagnosed leukemia patients including 24 acute myeloid leukemia (AML), 18 chronic myelogenous leukemia (CML), 6 acute lymphoblastic leukemia (ALL), 17 blast crisis of chronic myelogenous leukemia and 13 patients with iron deficiency anemia (IDA) were used as controls. The relative expression of gene gfi1 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and taqman quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). The results showed that gene expression of gene gfi1 in leukemia patients was obviously higher than that in controls and the difference was statistically significant (p < 0.01), in which the expression of gene gfi1 in newly diagnosed CML patients was higher than that in newly diagnosed AML, newly diagnosed ALL, CML-BCP patients and the difference was significant (p < 0.01). Expression of gene gfi1 in lymphocytic blast crisis of CML was higher than that in nonlymphocytic blast crisis of CML, and the difference was significant. It is concluded that gene gfi1 may play an important role in leukemia, especially in CML incidence and progression. The high level expression of gene gfi1 may be participate in the development of lymphoma.
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PMID:[Expression of growth-factor independence 1 in patients with leukemia and its significance]. 2072 83

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by translocation of genetic material from chromosome 9 to chromosome 22 to form a fusion gene (BCR-ABL1) that is responsible for abnormal tyrosine kinase activity and alteration of various downstream signaling pathways. In addition to morphological diagnosis of CML phase, it is essential to detect BCR-ABL1 fusion by either metaphase cytogenetics or reverse transcriptase polymerase chain reaction that also determines type of mRNA transcript. Once treatment begins, monitoring the response to Tyrosine Kinase Inhibitor (TKI) using standardized techniques and guidelines is important to check for failure of response and thus, plan timely intervention by increasing the dose of TKI or opting for second line TKIs. The goal is to stop evolution of CML to accelerated phase or blast crisis that has poor response to treatment. Also, it is desirable to achieve good outcomes and even treatment free remission in patients of CML on TKI. Thus, molecular monitoring by reverse transcriptase quantitative PCR (RT-qPCR) is done at regular intervals. There are international recommendations and quality control measures to standardize the reporting of fusion gene transcript levels by quantitative PCR (RT-qPCR) in CML to achieve and maintain sensitivity in molecular detection of CML disease burden. Various state-of-the-art molecular techniques have emerged to accurately determine the number of fusion-gene transcript levels. This review highlights various methodologies and their practical implications in management of CML patients on TKI.
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PMID:Laboratory Monitoring of Chronic Myeloid Leukemia in Patients on Tyrosine Kinase Inhibitors. 2962 60

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) characterized by the presence of a reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34:q11), resulting in fusion of the break point cluster region (BCR) with the ABL gene, which forms an oncogene, the transcript of which is an oncoprotein with a tyrosine kinase function. In the great majority of CML; BCR/ABL1 is cytogenetically visualized as t(9;22); giving rise to the Ph chromosome, harboring the chimeric gene. Cryptic or masked translocations occur in 2-10% patients with no evidence for the BCR/ABL rearrangement by conventional cytogenetics but are positive by Fluorescence in Situ Hybridization (FISH) and/or reverse transcriptase polymerase chain reaction (RT-PCR). These patients are described as Philadelphia negative (Ph negative) BCR/ABL1- positive CML with the chimeric gene present on the derivative chromosome 22, as in most CML cases, or alternatively on the derivative 9 in rare occasions. In the majority of cases, CML is diagnosed in the chronic phase; it is less frequently diagnosed in accelerated crises, and occasionally, its initial presentation is as acute leukemia. The prevalence of extramedullary blast phase (BP) has been reported to be 7-17% in patients with BP. Surprisingly, no extra-medullary blast crises of B- lymphoid lineage have been reported before among cases of CML as the initial presentation. We report an adult male diagnosed as CML- chronic phase when he was shortly presented with treatment-naive extramedullary B-lymphoid blast crises involving multiple lymph nodes, with no features of acceleration or blast crises in the peripheral blood (PB) and bone marrow (BM). In addition the patient had variant/cryptic Philadelphia translocation. This is the first report of CML, on the best of our knowledge, with extramedullary B-lymphoid blast phase, as initial presentation, that showed a cryptic Ph translocation.
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PMID:Chronic Myeloid Leukemia with cryptic Philadelphia translocation and extramedullary B-lymphoid blast phase as an initial presentation. 2963 32


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