Molecular monitoring and mutation analysis of patients with advanced phase CML and Ph plus ALL receiving dasatinib

• Published in: European journal of haematology 2010, Vol.85 (5), p.399
• Main Authors: Olsson-Strömberg, Ulla, Hermansson, Monica, Lundan, Tuija, Ohm, Anne-Charlotte, Engdahl, Ida, Höglund, Martin, Simonsson, Bengt, Porkka, Kimmo, Barbany, Gisela
• Format: Article
• Language: English
• Subjects: chronic myeloid leukemia; MEDICIN; MEDICINE; molecular monitoring; mutation
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/j.1600-0609.2010.01506.x

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.