From the monitoring of Bcr/Abl fusion gene level in patient with chronic myeloid leukemia
to the imatinib resistance detection – case report
Rohoň P.1, Faber E.1, Naušová J.2, Solná R.2, Rožmanová Š.1, Plachý R.1, Brejcha M.3, Jarošová M.1, Divoký V.2, Indrák K.1
1Hemato-onkologická klinika FN Olomouc a LF UP v Olomouci 2Ústav biológie LF UP v Olomouci 3Onkologické centrum J.G. Mendela, Nový Jičín |
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Summary:
There is the case report of 63-years old patient with Ph1 positive chronic myeloid leukaemia (CML) who is treated
with 400 mg of imatinib daily. It is because of the secondary cytogenetic resistance to interferon alpha after two years
from diagnosis. After initial cytogenetic response (10 % Bcr/Abl positive cells detected by bone marrow interphase
FISH examination after 3 months and 1 log decrease in quantitative RT-PCR after 6month of treatment) there is the
cytogenetic progression in one year with failure of the response to the escalated dosage 800 mg daily. It leads to the
suspicion of imatinib resistance. In vitro tests confirm it: there is a high expression of WT1 gene, the presence of
phosphorylated CRKL and detection of T315I mutation in Abl kinase domain. This article is aimed at detection of
imatinib resistance in case of suspicion and should also show the review of the new treatment modalities. The resistance
detection is important from clinical point of view. It allows to stop the therapy which is not useful and economically
demanding, on the other side it moves it to the application of the new tyrosine kinase inhibitors, allogenic
stem cell transplantation or to experimental treatment.
Key words:
Bcr/Abl fusion gene, WT1 gene, quantitative RT-PCR, tyrosine kinase inhibitors, T315I mutation
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