Original scientific paper

Clinical significance of T315I ABL kinase domain mutation detection in patients resistant to imatinib mesylate therapy

Ivana Horvat ; Division of Laboratory Diagnostics, University Hospital of Traumatology, Zagreb, Croatia
Margareta Radić Antolic ; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Renata Zadro ; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
Dubravka Sertić ; Hematology Division, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
Boris Labar ; Hematology Division, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia

Abstract

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 TKI is T315I. The aim of this study was to detect if the presence of T315I 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 T315I 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 T315I mutation detection.
Results:T315I was detected in 4out of 24 patients (17%). Calculated median bcr-abl/abl levels were 19%forT315I positive and 13%forT315I negative patients, but the difference was not statistically significant (P = 0.394).
Conclusions: T315I detection is essential in therapy approach for CML patients as the treatment of choice for T315I carriers is stem-cell transplantation.

Keywords

chronic myeloid leukemia; imatinib mesylate resistance; T315I mutation

Hrčak ID:

47852

URI

https://hrcak.srce.hr/47852

Publication date:

1.2.2010.

Article data in other languages: croatian

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