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Molecular monitoring and mutation analysis of patients with advanced phase CML and Ph+ ALL receiving dasatinib
Author(s) -
OlssonStrömberg Ulla,
Hermansson Monica,
Lundán Tuija,
Ohm AnneCharlotte,
Engdahl Ida,
Höglund Martin,
Simonsson Bengt,
Porkka Kimmo,
Barbany Gisela
Publication year - 2010
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2010.01506.x
Subject(s) - dasatinib , imatinib , myeloid leukemia , tyrosine kinase , mutation , nilotinib , medicine , abl , mutation testing , clone (java method) , cancer research , tyrosine kinase inhibitor , mutant , protein kinase domain , oncology , biology , dna , gene , genetics , cancer , receptor
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.