article · Journal of Investigative Medicine
Chronic myeloid leukaemia patients receiving imatinib therapy were evaluated to determine whether circulating levels of miR-146a can predict early treatment response. In a study comparing sixty leukaemia patients with twenty healthy controls, eighty per cent of patients achieved a satisfactory treatment response by day ninety. Circulating miR-146a levels were initially lower in leukaemia patients than in healthy individuals but rose significantly after fourteen days of imatinib therapy. Patients who responded well showed an inverse correlation between miR-146a levels and BCR-ABL expression at ninety days. Statistical analysis demonstrated that baseline BCR-ABL percentages and miR-146a levels at fourteen days served as significant predictors of early treatment success. Evaluating miR-146a expression at fourteen days accurately distinguished treatment responders from non-responders, highlighting its utility for early clinical monitoring.
Identifying which leukaemia patients will respond positively to standard drug therapies early in their care can prevent ineffective treatment and guide timely adjustments. Measuring circulating biomarkers such as miR-146a provides clinicians with an accessible, early indicator of whether a patient is likely to benefit from imatinib, potentially improving clinical monitoring and long-term management in chronic myeloid leukaemia.
This research demonstrates an early-stage diagnostic application for clinical pathology laboratories and diagnostic developers, using quantitative rt-PCR to assess early drug response in leukaemia patients. While tested in a small sixty-patient cohort, the methodology remains at an early research stage and requires further validation across larger populations and other tyrosine kinase inhibitors before it could support an approved commercial diagnostic test.
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This study aimed to investigate the prognostic role of circulating miR-146a in the prediction of early response to imatinib treatment in patients with chronic myeloid leukemia (CML). Sixty patients with CML and 20 healthy controls were recruited in this study. <i>BCR-ABL</i> was assessed by quantitative rt-PCR at days 0 and 90 of imatinib therapy. Circulating miR-146a levels were assessed by quantitative rt-PCR at days 0, 14 and 90 of imatinib therapy for patients and once for controls. At day 90 of treatment, treatment response was achieved in 48 patients (80.0%). Responders had significantly lower baseline Sokal score when compared with non-responders. They also had significantly lower <i>BCR-ABL</i> expression at day 90 of treatment. The circulating miR-146a level was significantly lower in patients with CML than in healthy subjects and showed a significant rise after 14 days of imatinib treatment and an inverse correlation with <i>BCR-ABL</i> expression levels at 90 days. Using multivariate logistic regression analysis, baseline <i>BCR-ABL (%</i>) (OR (95% CI) 1.09 (1.03 to 1.016), p=0.006) and miR-146a at 14 days (OR (95% CI) 0.002 (0.0 to 0.09), p=0.001) were significant predictors of treatment response. Using ROC curve analysis, it was found that miR-146a expression at 14 and 90 days could distinguish responders from non-responders (AUC (95% CI) 0.849 (0.733 to 0.928) and 0.867 (0.755 to 0.941), respectively). This study reported for the first time that measurement of the circulating miR-146a expression at 14 days can predict the early response to imatinib treatment in patients with CML. Thus, this work indicates that miR-146a should be investigated in the setting of treatment response to other tyrosine kinase inhibitors.
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DOI: 10.1136/jim-2020-001563
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