ASSOCIATION OF POLYMORPHISM IN THE ABCC2 GENE WITH RESPONSE TO IMATINIB-BASED THERAPY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN NORTHERN REGION OF BRAZIL

Introduction: Chronic myeloid leukemia (CML) is the excessive proliferation of granulocytic lineage cells of hematopoietic system, its main characteristic is the Philadelphia chromosome, which consists of the translocation of chromosomes 9 and 22, resulting in the expression of BCR- ABL with unregulated tyrosine kinase enzymatic activity. The CML main treatment is imatinib (IMB), a selective tyrosine kinase inhibitor. However, literature reports a failure of therapeutic response in 25% of patients during the treatment of CML, which may be associated with individual genetic variability. ABC family genes encode carrier proteins that mediate the transport of substances into cells, including drugs. Genetic polymorphisms that modify the functionality of proteins encoded by these genes are related to the resistance of various drugs used in clinical practice. So, investigating polymorphism in these gene may help elucidate the therapeutic failure of IMB. Objective: To analyze the rs717620 polymorphism in the ABCC2 gene as a possible marker of response to imatinib mesylate. Methodology: The study population consisted of 105 patients with CML treated with IMB at a reference hospital in oncology in Pará. Polymorphism genotyping was performed by real-time PCR using QuantStudio 12K Flex Real-Time PCR System (Applied Biosystems®, Foster City, California, USA). A panel of 61 Ancestral Information Markers was used for genomic control. Statistical analyzes were performed in the SPSS 23.0 program. Results: The results indicated that 7% of patients did not respond to the treatment. There was no statistical significance between the rs717620 polymorphism studied and the response to CML treatment (p = 0,187, OR = 1,103, CI = 1,026-1,186). Although our result, another studies found out that ABCC2 gene was associated with imatinib resistance and had a combined influence on both elimination and distribution of methotrexate, also a treatment to leukemias. These result vary according to the population studied and as ours is a very genetically different population, our research may have a great impact on literature. Conclusion: In conclusion, our data showed that the polymorphism studied in the ABCC2 gene is not statistically significant.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
23 October 2019