engleski

Influence of ABL1 mutations on therapy approach in CML patients who lost response to imatinib therapy

ABL1 mutations are the most important risk factor for the tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to analyse the influence of detected ABL1 mutations on the outcome of patients who lost response to imatinib therapy. The study included 9 CML patients (6M/3F), median age at diagnosis 55 years (range 34-65) on initial imatinib therapy. Patients were regularly followed up every 3 months by RQ-PCR bcr-abl1 measurement. Sanger sequencing was performed on cDNA for mutation detection. Only 2 patients achieved MMR at the time point of mutation detection. Median period from diagnosis until mutation detection was 35 months (range 12- 165). In total, 10 mutations were detected: G250E in 3 patients, Y253H in 2 patients, M244V, L364I and F359V in 1 patient each, E355G and F359C in the same patient. Median RQ-PCR bcr-abl1 level at the time point of mutation detection was 5.63% IS (range 0.2440-18.09). To investigate the time point of mutation appearance diagnostic samples from 3 patients who did not achieve adequate imatinib response were screened for mutations and no mutation was found. For 4 patients mutations were screened in preceding samples (3-6 months before) and mutation was detected in one patient sample only. Based on detected mutations, therapy was changed to second generation TKI ; two patients, because of intolerance or resistance, switched to hydroxyurea. In follow up, there was no response in 6 patients while 3 patients responded adequately to therapy change. In conclusion, mutation detection in CML patients at the right moment could bring benefit in therapy management for the patient but there are other biological factors that influence individual therapy approach.

abl1 mutation; tyrosine kinase inhibitor; therapy resistance

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