Journal of Applied Genetics 49(2), 2008, pp. 201-203

Dasatinib treatment can overcome imatinib and nilotinib resistance in CML patient carrying F359I mutation of BCR-ABL oncogene

Marta Baranska, Krzysztof Lewandowski, Michal Gniot, Malgorzata Iwola, Maria Lewandowska, Mieczyslaw Komarnicki

Abstract: Point mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading to imatinib resistance the second generation of tyrosine kinase inhibitors (TKI- e.g. nilotinib or dasatinib) may be effective. Here, we report a case of a CML patient who during imatinib treatment did not obtain clinical and cytogenetic response within 12 months of therapy. The sequencing of BCR-ABL kinase domains was performed and revealed the presence of a F359I point mutation (TTC-to-ATC nucleotide change leading to Phe-to-Ile amino acid substitution). After 1 month of nilotinib therapy a rapid progression of clinical symptoms was observed. In the presence of the F359I point mutation only dasatinib treatment overcame imatinib and nilotinib resistance

Key words: BCR-ABL oncogene, chronic myeloid leukemia, direct sequencing, F359I point mutation, kinase inhibitors.

Correspondence: M. Baranska, Department of Hematology, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland; e-mail: marta.baranska@onet.eu