RRML - Identification of second generation tyrosine kinase inhibitors relevant mutations in a cohort of chronic myeloid leukemia patients treated in a single center in Romania
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Dr. Adrian Man
   
 
Nr. 19(3)/2011
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Identification of second generation tyrosine kinase inhibitors relevant mutations in a cohort of chronic myeloid leukemia patients treated in a single center in Romania

Kinga Tatar, Rodica Talmaci, Dumitru Jardan, Maria Damian, Adriana Coliță, Hortensia Ioniță, Coriu Daniel


Abstract:

Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired imatinib (IM) resistance in patients with chronic myeloid leukemia (CML), however there are large variances in the literature regarding the frequency of identified mutations in different cohort of patients and data originating from Romania are missing. Here we examine the frequency of tyrosine kinase mutations in the first cohort of Romanian CML patients, (all patients have been treated in Fundeni Clinical Institute). We used the technique of semi-nested polymerase chain reaction (PCR) for the amplification of the KD of BCR-ABL fusion gene, followed by direct sequencing (Sanger method).We also assessed the clinical relevance of the identified mutations and the proportion of patients in which mutational testing had led to a clinical decision. In our very heterogeneous cohort of patients only one fifth of patients had identifiable mutations and only 2 patients, representing 6.25 % of all tested patients and 28.5% from patients with identified mutations had a second generation tyrosine kinase inhibitor (SGI) clinically relevant mutations. In a recent cohort of patients with mutations from Adelaide, Australia, 166 of 386 (43%) had one or more SGI clinically relevant mutations. The technique of mutational testing of BCR-ABL kinase domain remains a highly valuable method for evaluating/predicting the therapeutic response of CML patients. Its value is significantly enhanced by the appropriate selection of the patients referred for this examination.

Keywords: mutations,chronic myeloid leukemia,tyrosine kinase inhibitors,resistance

 
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How to cite
Tatar K, Talmaci R, Jardan D, Damian M, Coliță A, Ioniță H, et al. Identification of second generation tyrosine kinase inhibitors relevant mutations in a cohort of chronic myeloid leukemia patients treated in a single center in Romania. Rev Romana Med Lab. 2011;19(3):279-87