PS1170 INFLUX/EFFLUX TRANSPORTERS IN CHRONIC MYELOID LEUKEMIA: THE INFLUENCE OF GENETIC VARIANTS ON SUSCEPTIBILITY AND DRUG RESPONSE

Background: The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) is consider a clinical success, however TKI resistance constitute a clinical problem. Drug resistance can be associated with several mechanisms, which could alter drug target and/or impact drug access...

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Published in:HemaSphere 2019-06, Vol.3 (S1), p.532-n/a
Main Authors: Alves, R.S., Gonçalves, A., Jorge, J., Marques, G., Ribeiro, A. Barbosa, Tenreiro, R., Coucelo, M., Diamond, J., Pereira, A., Freitas‐Tavares, P., Almeida, A.M., Sarmento‐Ribeiro, A.B.
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Language:English
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Summary:Background: The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) is consider a clinical success, however TKI resistance constitute a clinical problem. Drug resistance can be associated with several mechanisms, which could alter drug target and/or impact drug access to target. TKI resistance mechanisms include mutations of the BCR‐ABL gene and changes on influx and efflux transporters, which affect intracellular drug concentrations. Influx (like OCT1, OCTN2) and efflux transporters (as PgP, BCRP) comprise a variety of proteins express on cell and/or organelles membranes responsible for, respectively, the intrusion or extrusion of substrates, as nutrients, metabolic products, xenobiotics and chemotherapy. Since influx and efflux transporters mediate the intake and extrusion of TKIs, genetic variants on these genes could affect their function and modulate treatment response, as well as influence cancer development. Aims: In this work, we explore the impact of genetic variability (as single nucleotide polymorphisms, SNPs) in genes related with drug transport (ABCB1, ABCG2, SLC22A1 and SLC22A5) on CML susceptibility, drug response and BCR‐ABL mutation status. Methods: In 198 CML patients and 404 controls, ten genetic variants in ABCB1, ABCG2, SLC22A1 and SLC22A5 were genotyped by tetra‐primers‐AMRS‐PCR. The role of these SNPs in CML susceptibility and their association with clinical and laboratory characteristics as well as with therapy response was assessed by logistic regression analysis and/or by Fisher's exact test, with p 
ISSN:2572-9241
2572-9241
DOI:10.1097/01.HS9.0000562964.05114.68