Role of Pre Therapeutic Expression of Human Organic Cation Transporter1 SLC22A1 Gene in Predicting Clinical Outcome in Imatinib Treated CP CML Patients

Background Human organic cation transporter1 hOCT1, SLC22A1 , an influx transporter,is responsible for the uptake of Imatinib into chronic myelod leukemia CML cells. Some patients fail to achieve optimal molecular response to Imatinib, defined as major molecular response MMR i.e.BCR ABL 1 = 0.1 within 12 months of therapy. Pretherapeutic expression of hOCT1 may be beneficial in predicting the response to imatinib in CML patients. Methodology 30 newly diagnosed BCR ABL positive CML patients in chronic phaseand30 healthy control subjects, all ethnic Indians ,were recruited in the study. hOCT1 gene expression in PBMCs was quantified by SYBR Green based qRT PCR, using the 2 DDCt method. After initiation of imatinib therapy, hematological response was monitored at regular intervals, and molecular response BCR ABL1 ABL1 ratio assessed after 6 or 12 months. Results and discussion The cases were divided into two groups, high expression n=15 and low expression n=15 groups, based on the median value of fold change in hOCT1 gene expression. Median =5.6 . 11 73.33 patients with low expression achieved CHR by the end of 3 months, whereas 4 26.66 did not. On the contrary, all 15 patients 100 with high hOCT1 gene expression achieved CHR by the end of 3 months. p=0.10 .It was also observed that the mean THR time to CHR in low expression group was higher than in high expression group. p=0.046 It was seen that while all 15 patients with high expression had an optimal response , only 13.33 n=2 patients with low expression had it. In the low expression group, 40 patients had treatment failure n=6 while remaining 23.33 n=7 were categorized as warning. p=0.000 ELN 2013 guidelines Conclusions Hence it was concluded that high expression of hOCT1 gene leads to early achievement of CHR. In case of molecular response, it was observed that high expression of hOCT1 gene was significantly associated with achievement of on optimal response to imatinib. These findings emphasize that knowledge of pretherapeutic level of hOCT1 could be a useful marker to predict imatinib therapy outcome in CML patients, and the prospects of personalized therapy in such patients. Namrata Bhutani | Deepika Arora | Neha Bhutani "Role of Pre-Therapeutic Expression of Human Organic Cation Transporter1 (SLC22A1) Gene in Predicting Clinical Outcome in Imatinib Treated CP-CML Patients" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-4 | Issue-4 , June 2020, URL: https://www.ijtsrd.com/papers/ijtsrd31316.pdf Paper Url :https://www.ijtsrd.com/biological-science/biochemistry/31316/role-of-pretherapeutic-expression-of-human-organic-cation-transporter1-slc22a1-gene-in-predicting-clinical-outcome-in-imatinib-treated-cpcml-patients/namrata-bhutani