Abstract
Background: A significant number of CML patients relapse after discontinuation of therapy, even after achieving DMR, which calls for a need of early biomarkers to discontinue therapy. miRs have a vital role in pathways that decide the pharmacokinetics and pharmacodynamics displayed by a particular patient. Therefore, in this study, we studied the role of miRs to achieve DMR by CML patients on imatinib therapy.
Methodology: CML patients were categorized in to two groups DMR and without DMR. 4 patients in each group were screened for differential expression of miRs through micro array platform. The differentially expressed miRs were selected for further validation in a large cohort of CML patients.
Results: We identified 15 miRs through micro array which were differentially expressed among CML patients with DMR and without DMR. Among these 15 miRs, miR-4746-3p, after multiple correction, was found to be significantly, p=0.001, overexpressed in without DMR group. Therefore, miR-4746 was selected for further validation in a large cohort of CML patients on imatinib therapy. We found that there was a significant difference in miR-4746 expression among CML patients with DMR and without DMR groups. miR-4746 levels were significantly (p=0.003) elevated in without DMR group as compared to DMR group. Next, we analyzed miR-4746 expression in 50 newly diagnosed CML patients before starting imatinib therapy and monitored their response to imatinib therapy at 6 and 12 months of the therapy. We found that those patients who had high levels, higher than the cut of miR-4746 expression in without DMR group = 2.62 fold, of miR-4746 tend to be in without DMR or achieve DMR at a later stage compared to CML patients who had lower miR-4746 levels, lower than 2.63 fold, who tend to achieve DMR on imatinib therapy.
Conclusion: miR-4746 may be used as a biomarker to select for CML patients who can qualify for achieving DMR and can be considered for imatinib discontinuation trial.