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Keywords {🔍}

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Topics {✒️}

chronic myeloid leukaemia bcr-abl1/gusb ratio relative real-time quantitative pcr high bcr-abl1 levels 1 µl uracil-dna-glycosidase georg-nikolaus franke atypical bcr-abl1 transcripts atypical bcr-abl1 transcript atypical bcr-abl1 fusions bcr-abl1 transcript types bcr-abl1 fusion transcript rare bcr-abl1 transcript rna quality early bcr-abl1 decline bcr-abl1/gusb ratios ratio bcr-abl1/gusb bcr-abl fusion mrnas bcr-abl fusion proteins named exons b1–b5 eutos cooperative network e1a2 bcr-abl1 transcripts e1a2 bcr-abl1 transcript bcr-abl1 transcript e1a2 e19a2 bcr-abl1 transcript e13a3 bcr-abl1 transcript bcr-abl1 fusion gene e14a3 bcr-abl1 transcript e8a2 bcr-abl1 transcript chimeric bcr-abl1 protein bcr-abl gene variants bcr-abl fusion gene bcr-abl1-positive patients bcr-abl1 negative patient bcr-abl mrna quantification largest chimeric bcr-abl1 chronic myeloid leukemia e13a3 bcr-abl fusion stem cell transplantation bcr-abl1 transcripts located double transcript e13a3/e14a3 bcr-abl1 transcripts detected breakpoint cluster region-abelson avoid false-negative results article download pdf e6a2 bcr-abl transcript 19 µl pcr mix bcr-abl expression based m-mlv reverse transcriptase /µl taq polymerase bcr-abl1 levels

Questions {❓}

• Colla S, Sammarelli G, Voltolini S, Crugnola M, Sebastio P, Giuliani N (2004) e6a2 BCR-ABL transcript in chronic myeloid leukemia: is it associated with aggressive disease?

Schema {🗺️}

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         headline:Assessment of individual molecular response in chronic myeloid leukemia patients with atypical BCR-ABL1 fusion transcripts: recommendations by the EUTOS cooperative network
         description:Approximately 1–2% of chronic myeloid leukemia (CML) patients harbor atypical BCR-ABL1 transcripts that cannot be monitored by real-time quantitative PCR (RT-qPCR) using standard methodologies. Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated robust RT-qPCR methods for these patients. BCR-ABL1 transcripts were amplified and sequenced to characterize the underlying fusion. Residual disease monitoring was carried out by RT-qPCR with specific primers and probes using serial dilutions of appropriate BCR-ABL1 and GUSB plasmid DNA calibrators. Results were expressed as log reduction of the BCR-ABL1/GUSB ratio relative to the patient-specific baseline value and evaluated as an individual molecular response (IMR). In total, 330 blood samples (2–34 per patient, median 8) from 33 CML patients (19 male, median age 62 years) were analyzed. Patients expressed seven different atypical BCR-ABL1 transcripts (e1a2, n = 6; e6a2, n = 1; e8a2, n = 2; e13a3, n = 4; e14a3, n = 6; e13a3/e14a3, n = 2; e19a2, n = 12). Most patients (61%) responded well to TKI therapy and achieved an IMR of at least one log reduction 3 months after diagnosis. Four patients relapsed with a significant increase of BCR-ABL1/GUSB ratios. Characterization of atypical BCR-ABL1 transcripts is essential for adequate patient monitoring and to avoid false-negative results. The results cannot be expressed on the International Scale (IS) and thus the common molecular milestones and guidelines for treatment are difficult to apply. We, therefore, suggest reporting IMR levels in these cases as a time-dependent log reduction of BCR-ABL1 transcript levels compared to baseline prior to therapy.
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      headline:Assessment of individual molecular response in chronic myeloid leukemia patients with atypical BCR-ABL1 fusion transcripts: recommendations by the EUTOS cooperative network
      description:Approximately 1–2% of chronic myeloid leukemia (CML) patients harbor atypical BCR-ABL1 transcripts that cannot be monitored by real-time quantitative PCR (RT-qPCR) using standard methodologies. Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated robust RT-qPCR methods for these patients. BCR-ABL1 transcripts were amplified and sequenced to characterize the underlying fusion. Residual disease monitoring was carried out by RT-qPCR with specific primers and probes using serial dilutions of appropriate BCR-ABL1 and GUSB plasmid DNA calibrators. Results were expressed as log reduction of the BCR-ABL1/GUSB ratio relative to the patient-specific baseline value and evaluated as an individual molecular response (IMR). In total, 330 blood samples (2–34 per patient, median 8) from 33 CML patients (19 male, median age 62 years) were analyzed. Patients expressed seven different atypical BCR-ABL1 transcripts (e1a2, n = 6; e6a2, n = 1; e8a2, n = 2; e13a3, n = 4; e14a3, n = 6; e13a3/e14a3, n = 2; e19a2, n = 12). Most patients (61%) responded well to TKI therapy and achieved an IMR of at least one log reduction 3 months after diagnosis. Four patients relapsed with a significant increase of BCR-ABL1/GUSB ratios. Characterization of atypical BCR-ABL1 transcripts is essential for adequate patient monitoring and to avoid false-negative results. The results cannot be expressed on the International Scale (IS) and thus the common molecular milestones and guidelines for treatment are difficult to apply. We, therefore, suggest reporting IMR levels in these cases as a time-dependent log reduction of BCR-ABL1 transcript levels compared to baseline prior to therapy.
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         Chronic myeloid leukemia
         CML
          BCR-ABL1
         Atypical transcripts
         Molecular monitoring
         Oncology
         Cancer Research
         Internal Medicine
         Hematology
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            type:Organization
      name:Nicholas C. P. Cross
      affiliation:
            name:Salisbury NHS Foundation Trust
            address:
               name:Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK
               type:PostalAddress
            type:Organization
            name:University of Southampton
            address:
               name:School of Medicine, University of Southampton, Southampton, UK
               type:PostalAddress
            type:Organization
      name:Andreas Hochhaus
      affiliation:
            name:Universitätsklinikum Jena
            address:
               name:Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
               type:PostalAddress
            type:Organization
      name:Thomas Ernst
      url:http://orcid.org/0000-0003-2147-489X
      affiliation:
            name:Universitätsklinikum Jena
            address:
               name:Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
      name:Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK
      name:Faculty of Medicine, Imperial College London, London, UK
      name:Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
      name:III. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany
      name:Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany
      name:Bergonie Institute Cancer Center Bordeaux, INSERM U1218, University of Bordeaux, Bordeaux, France
      name:Hematology Department, Fundeni Clinical Institute, University of Medicine and Pharmacy ‘Carol Davila’, Bucharest, Romania
      name:Hematopathology Unit, Department of Pathology, University of Barcelona, Barcelona, Spain
      name:Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology “Lorenzo e Ariosto Seràgnoli”, University of Bologna, Bologna, Italy
      name:Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
      name:Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK
      name:School of Medicine, University of Southampton, Southampton, UK
      name:Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
      name:Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

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