Prospective BCR-ABL analysis by polymerase chain reaction (RT-PCR) in adult acute B-lineage lymphoblastic leukemia: reliability of RT-nested-PCR and comparison to cytogenetic data

Gleißner, Beate; Rieder, Harald; Thiel, E.; Fonatsch, Christa; Janssen, L. A. J.; Heinze, B; Janssen, J. W. G.; Schoch, Claudia; Goekbuget, Nicola; Mäurer, J.; Hoelzer, Dieter; Bartram, Claus R.

doi:10.1038/sj.leu.2402304

Cited by 27 publications

(16 citation statements)

References 29 publications

(27 reference statements)

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“…This genetic aberration is found in B25% of adult patients and in 5% of children with ALL and is associated with a poor prognosis. 34,37 In B70% of patients with Ph þ ALL, the break point in the BCR gene is located in the first exon of the BCR gene (e1) and is juxtaposed to the second exon of the ABL gene (a2). The resultant minor break-point transcript (e1-a2) encodes a 190-kDa chimeric protein (p190).…”

Section: Pcr Analysis Of Bcr-abl Transcriptsmentioning

confidence: 99%

“…The second most frequent fusion transcript involves break points in a 5.8-kb region spanning exons 12-16, known as the major break-point cluster region (M-bcr) and is typical of chronic myeloid leukemia (CML) but is also seen in 30% of patients with Ph þ ALL. 34,36,37,56 Detection of BCR-ABL fusion transcripts by reverse transcription PCR is relevant not only for diagnostic purposes but also in particular for quantitative monitoring of MRD. 34 Several studies have shown that levels of MRD in the bone marrow (BM) of patients with Ph þ ALL, assessed by RQ-PCR after induction and after consolidation treatment, is a powerful indicator of prognosis.…”

Section: Pcr Analysis Of Bcr-abl Transcriptsmentioning

confidence: 99%

“…34,36,37,56 Detection of BCR-ABL fusion transcripts by reverse transcription PCR is relevant not only for diagnostic purposes but also in particular for quantitative monitoring of MRD. 34 Several studies have shown that levels of MRD in the bone marrow (BM) of patients with Ph þ ALL, assessed by RQ-PCR after induction and after consolidation treatment, is a powerful indicator of prognosis. 14,15,18,20,21,27 This also applies to the posttransplant setting, in which sequential analysis of patients who received allogeneic stem cell transplantation showed that repeated PCR positivity correlated with an increased risk of relapse.…”

Section: Pcr Analysis Of Bcr-abl Transcriptsmentioning

confidence: 99%

“…Flow cytometric and molecular methods that allow sensitive detection and specific quantification of residual leukemic cells have been developed. [28][29][30][31][32][33][34][35][36][37][38][39][40] Standardization of methodologies and definitions of common MRD terms become increasingly important, not only to ensure comparability of MRD data between different MRD laboratories within a single MRD-based treatment protocol but also to provide a sound basis for the comparison of MRD results between different treatment protocols, including those that evaluate the effectiveness of new agents.…”

Section: Introductionmentioning

confidence: 99%

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Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008

et al. 2009

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Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR-and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols.

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Section: Pcr Analysis Of Bcr-abl Transcriptsmentioning

confidence: 99%

Section: Pcr Analysis Of Bcr-abl Transcriptsmentioning

confidence: 99%

Section: Pcr Analysis Of Bcr-abl Transcriptsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008

et al. 2009

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“…32 Such cross-contamination is difficult to recognize, as fusion gene transcripts, although leukemia-specific, are not patient-specific markers. Also the levels of fusion gene transcripts can vary significantly between patients.…”

Section: Rq-pcr-based Quantification Of Leukemia-associated Fusion Genesmentioning

confidence: 99%

Why and how to quantify minimal residual disease in acute lymphoblastic leukemia?

Szczepański

2007

Leukemia

114

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Several studies have demonstrated that monitoring of minimal residual disease (MRD) in childhood and adult acute lymphoblastic leukemia (ALL) significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of early treatment response and consequently for improved front-line therapy stratification. MRD information is also significant for children undergoing allogeneic hematopoietic stem cell transplantation and those with relapsed ALL. Currently, three highly specific and sensitive methodologies for MRD detection are available, namely multiparameter flow cytometric immunophenotyping, real-time quantitative polymerase chain reaction (RQ-PCR)-based detection of fusion gene transcripts or breakpoints, and RQ-PCR-based detection of clonal immunoglobulin and T-cell receptor gene rearrangements. In this review, characteristics, pitfalls, advantages and disadvantages of each MRD technique are critically discussed. The special emphasis is put on interlaboratory standardization, especially in view of the results obtained within the European collaborative BIOMED-1, BIOMED-2, and Europe Against Cancer projects and recent developments by European Study Group on MRD detection in ALL and EuroFlow Consortium. Standardized MRD techniques form the basis for stratification of patients into the risk groups in new treatment protocols mainly in childhood ALL. Only the results of these studies can answer the question whether MRD-based treatment intervention is associated with improved outcome. Leukemia ( The rationale for detection of MRD in ALL The concept of minimal residual disease (MRD) detection in acute lymphoblastic leukemias (ALL) is inherently associated with the progress in treatment of these malignancies. 1 More than 80% of childhood and 35% of adult ALL patients can be cured with modern chemotherapy supplemented with hematopoietic stem cell transplantation (HSCT) in high risk patients (reviewed by Hoelzer et al. 2 ). Still, a substantial number of ALL patients relapse and the prediction of relapse with conventional prognostic factors such as age, blast count at diagnosis, immunophenotype at diagnosis, presence of chromosome aberrations, response to steroid prophase and classical clinical risk group assignment is far from optimal. Also microarray-based gene expression profiling could not identify gene signatures, typically associated with high risk of relapse. Tracing residual leukemic cells during early phases of treatment provides prognostic information superior to all known classical prognostic factors. Several prospective studies in childhood ALL demonstrated that the most relevant information comes from detection of MRD in bone marrow at the early phases of treatment, particularly at the end of induction treatment (reviewed by Szczepań ski et al. 3 and Cazzaniga and Biondi 4 ). Children with undetectable MRD at the end of induction have an excellent prognosis and are good candidates for treatment de-intensification or at least should not be subjected to further treatment intensificat...

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B‐Cell Neoplasms

Valli¹

2007

Veterinary Comparative Hematopathology

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Prospective BCR-ABL analysis by polymerase chain reaction (RT-PCR) in adult acute B-lineage lymphoblastic leukemia: reliability of RT-nested-PCR and comparison to cytogenetic data

Cited by 27 publications

References 29 publications

Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008

Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008

Why and how to quantify minimal residual disease in acute lymphoblastic leukemia?

B‐Cell Neoplasms

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