BCR-ABL mutation analysis allovos to provide „tailored therapy” for CML patients resistant to imatinib
Authors:
M. Šťastný 1; K. Machová Poláková 2; H. Klamová 2; D. Žáčková 3; J. Voglová 4; M. Karas 5; J. Moravcová 2; E. Faber 6
Authors‘ workplace:
Bristol-Myers Squibb Czech Republic, 2Ústav hematologie a krevní transfuze Praha, 3Interní hematoonkologická klinika FN a LF Masarykovy univerzity Brno, 4II. interní klinika – oddělení klinické hematologie, LF UK a FN Hradec Králové, 5Hematologicko-onkolo
1
Published in:
Transfuze Hematol. dnes,16, 2010, No. 1, p. 47-54.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
Chronic myeloid leukemia (CML) becomes a disease, treatment of which represents typical example of tailored therapy. Despite the fact that first line therapy of CML using imatinib revolutionized the treatment of this disease, it became clear that during 5 years 25–35 % of the patients require change in the therapy due to the development of imatinib resistance or intolerance. The most frequent mechanism responsible for imatinib resistance is development of mutation in BCR-ABL kinase domain. Mutations cause different level of imatinib resistance and while some of them can be overcome by increased dose of imatinib (M351T), others seem to be resistant to nilotinib (P-loop mutations, F359C/V) and others are more resistant to dasatinib (F317L/V a V299L). This review is focused only to clinically most important mutations occurring in 15 amino-acid substitutions, which account for more than 85 % of all BCR-ABL mutations. It has been shown recently that advances in molecular methods enable to better understand disease itself, weigh the benefit to risk ratio of the therapy, individualize therapeutic approach and eventually adjust CML therapy earlier in order to minimize the risk of CML progression to advanced phases.
Key words:
chronic myeloid leukemia, tyrosine kinase inhibitors, imatinib, dasatinib, nilotinib, BCR-ABL domain mutations, imatinib resistance, tailored therapy
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