Quantitative BCR-ABL1 RQ-PCR fusion transcript monitoring in chronic myelogenous leukemia

Franklin R. Moore, Carole B. Rempfer, Richard D. Press

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

The reciprocal Philadelphia translocation between chromosomes 9 and 22 [t(9;22)(q34;q11)] creates a BCR-ABL1 fusion protein that occurs in approximately 95% of cases of chronic myelogenous leukemia (CML), 15% of cases of adult acute lymphoblastic leukemia, and 5% of adult cases of acute myeloid leukemia. The BCR-ABL1 protein is a constitutively activated tyrosine kinase that induces and maintains the neoplastic phenotype in these leukemias. PCR-based methods to identify and quantitate the tumor-specific BCR-ABL1 RNA have been shown to be an ultrasensitive diagnostic/prognostic tool for Philadelphia-positive leukemias. A novel tyrosine kinase inhibitor (TKI), imatinib, has been confirmed as an effective targeted treatment in most CML patients. A consensus goal for TKI treatment is to achieve a major molecular response (MMR), defined as a 3-log (1,000-fold) reduction in BCR-ABL1 transcripts. Patients who achieve an MMR have been shown to have a significantly reduced risk of disease progression. Conversely, increasing post-therapy BCR-ABL1 RNA levels convey a significantly increased risk of disease progression. The early identification of these high-risk patients may allow early changes to the therapeutic strategy, before frank relapse. Thus, quantitative measurement of BCR-ABL1 transcripts in blood and bone marrow both aids in the initial diagnosis of CML and is essential for routine post-therapy minimal residual disease monitoring. We describe here a method for quantitating BCR-ABL1 transcripts in peripheral blood or bone marrow of CML patients using real-time quantitative reverse transcription PCR (RQ-PCR).

Original languageEnglish (US)
Title of host publicationHematological Malignancies
Pages1-23
Number of pages23
DOIs
StatePublished - Sep 4 2013

Publication series

NameMethods in Molecular Biology
Volume999
ISSN (Print)1064-3745

Keywords

  • BCR-ABL1
  • Chronic myelogenous leukemia
  • Imatinib
  • Major molecular response
  • Philadelphia chromosome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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    Moore, F. R., Rempfer, C. B., & Press, R. D. (2013). Quantitative BCR-ABL1 RQ-PCR fusion transcript monitoring in chronic myelogenous leukemia. In Hematological Malignancies (pp. 1-23). (Methods in Molecular Biology; Vol. 999). https://doi.org/10.1007/978-1-62703-357-2-1