Gene expression analysis of efflux and influx (oct1) transporters in different cml phases

Research Article
Akash Pandey and Dr. Priyanka Singh
DOI: 
http://dx.doi.org/10.24327/ijrsr.20251611.0104
Subject: 
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KeyWords: 
CML, influx, drug entry, BCR-ABL1
Abstract: 

The Philadelphia (Ph) chromosome is produced by the reciprocal translocation of chromosomes 9 and 22, which is a hallmark of chronic myeloid leukaemia (CML), a clonal myeloproliferative illness. Organic cation transporter 1 (OCT-1) and organic cation/carnitine transporter 2 (OCTN2) are two membrane transporters that are necessary for the entry of imatinib into cells. Consequently, as their low expression lowers the intracellular imatinib concentration, membrane transporters have also been identified as significant factors to poor treatment response. Consequently, OCT-1, the primary influx transporter implicated in imatinib absorption in CML cells, has been identified as a critical predictor of intracellular imatinib levels attained in cells that contribute to imatinib resistance in CML patients. Investigating the gene expression of key transporters, such as P-glycoprotein (Pg-P), Multidrug Resistance Protein 1 (MRP1), Lung Resistance Protein (LRP), and Breast Cancer Resistance Protein (BCRP), during various stages of chronic myeloid leukaemia (CML) and following treatment was the aim of this study. There were five healthy controls and 120 patients with chronic myeloid leukaemia (CML). Depending on their diagnosis, the patients were grouped. Thirty patients had breast cancer, thirty had accelerated phase, thirty had blastic crisis, thirty had aphasia, thirty had chronic pain, and thirty had chronic CML. Imatinib (N=58), hydrea (N=32), or a combination of the two (N=30) were administered to the patients. Using matched blood and bone marrow samples, gene expression analysis was carried out to assess MDR marker expression throughout a range of disease stages and therapeutic approaches. The results provide insight on the mechanisms behind transporter-mediated drug resistance and might help improve CML patients’ treatment regimens.