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Molecular monitoring and mutation analysis of patients with advanced phase CML and Ph plus ALL receiving dasatinib
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. (Hematologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 85, no 5, 399-404 p.Article in journal (Refereed) Published
Abstract [en]

As a result of the excellent responses achieved in chronic phase chronic myeloid leukemia since the introduction of imatinib, sensitive techniques such as reverse transcriptase real-time PCR are warranted to monitor patients receiving tyrosine kinase inhibitors (TKI). Our objective was to determine the value of molecular monitoring Ph-positive leukemias under dasatinib treatment. We used real-time PCR and ABL1 kinase domain sequencing on sequential samples from 11 patients with Philadelphia-positive leukemias who received dasatinib. We were able to detect pre-existing mutations in the kinase domain of BCR-ABL1 in four patients, particularly in patients with high BCR-ABL1 transcript levels. Most mutations disappeared with dasatinib, however, in five patients a clone with T315I appeared during dasatinib treatment. We conclude that sensitive molecular monitoring with real-time PCR for BCR-ABL1 transcripts and mutation screening of the ABL1 kinase domain of patients with Philadelphia-positive leukemias are valuable for patient management, however, mutation findings should be interpreted with caution, as mutant clones not always behave in vivo as predicted by in vitro assays.

Place, publisher, year, edition, pages
2010. Vol. 85, no 5, 399-404 p.
Keyword [en]
chronic myeloid leukemia, mutation, molecular monitoring
National Category
Medical and Health Sciences Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-133819DOI: 10.1111/j.1600-0609.2010.01506.xISI: 000283376500003OAI: oai:DiVA.org:uu-133819DiVA: diva2:371360
Available from: 2010-11-19 Created: 2010-11-16 Last updated: 2017-12-12Bibliographically approved

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