'Gatekeeper' mutation in patients with chronic myeloid leukemia resistant to imatinib therapy: effect on survival
Mohamed A.M El-Menoufy, Amel A El Naggar, Laila E.S Ziada
Department of Haematology, Medical Research Institute, Alexandria University, Alexandria, Egypt
Mohamed A.M El-Menoufy
Department of Hematology, Medical Research Institute, Alexandria 21561
DOI: 10.4103/ejh.ejh_18_18
Background T315I is the most difficult type of point mutation that appears during treatment of chronic myeloid leukemia (CML). It represents kind of a 'gatekeeper' that controls access of small molecule inhibitors and confers resistance to the most known tyrosine kinase inhibitors. Aim The aim of the present study was to assess the characteristics of Egyptian patients with CML harboring T315I mutation and to evaluate its effect on the patients' survival. Patients and methods A total of 45 patients with CML in chronic phase resistant to imatinib mesylate (IM) treatment were enrolled in this study. Allele-specific oligonucleotide-PCR was used to detect T315I BCR-ABL gene mutation in all patients at the time of IM resistance. Results T315I mutation was present in 11 (24.4%) patients. The level of resistance was heterogeneous. Responses were observed in two resistant T315+ patients with IM dose escalation and three patients who were shifted to second-generation tyrosine kinase inhibitor. There was no significant difference in patient characteristics and overall survival between T315I+ and T315I− resistant patients. Overall survival is significantly associated with the duration of response and the phase of the disease at the time of resistance. Conclusion Evaluation of T315I mutation is recommended in all patients with CML, even in the early phase of the disease, which may be subsequently associated with resistance or progression of their disease in the future and requires the need for an alternative therapeutic option(s).
El-Menoufy MA
El Naggar AA
Ziada LE
gatekeeper mutation
imatinib resistance
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