Klinička značajnost otkrivanja mutacije T31 51 u domeni ABL kinaze kod bolesnika rezistentnih na liječenje imatinib mesilatom

Horvat, Ivana; AntoIic, Margareta Radic; Zadro, Renata; Sertic, Dubravka; Labar, Boris
April 2010
Biochemia Medica;2010, Vol. 20 Issue 1, p75
Academic Journal
Background: Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of bcr-abl fusion gene and consequently bcr-abl fusion protein. Although the discovery of tyrosine kinase inhibitor (TKI), imatinib mesylate (IM), improved the treatment of CML patients, a proportion of patients develop resistance to the drug resulting in increased bcr-abl level. One of possible reasons for resistance are the mutations in ABL kinase domain. Some mutations can be overcome by increasing the drug dose or by using the new generation of TKI. The only mutation resistant to currently available IKI is T3151. The aim of this study was to detect if the presence of T3151 in patients resistant to imatinib mesylate therapy is associated with the increase or constantly high bcr-abl level. We also aimed to assess the possible difference in bcr-abl level in imatinib-resistant patients with and without T3151 mutation. Materials and methods: The study included 24 CML patients with inadequate response to IM therapy. Real time quantitative PCR was performed according to Europe Against Cancer protocol and allele specific oligonucleotide PCR was used for T3151 mutation detection. Results: 13151 was detected in 4 out of 24 patients (17%). Calculated median bcr-abl/abl levels were 19% for T3151 positive and 13% for T3151 negative patients, but the difference was not statistically significant (P = 0.394). Conclusions: T3151 detection is essential in therapy approach for CML patients as the treatment of choice for T3151 carriers is stem-cell transplantation.


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