Biomarkers for BCR-ABL1 as a Potential Therapeutic Option Among Adult Chronic Myeloid Leukaemia Treated With Tyrosine Kinase Inhibitors at Molecular Response in Multi-racial Malaysia: Hsa-mir-181a-5p for Decrement; hsa-mir-182-5p and hsa-mir-26a-5p for Increment.

Abstract BackgroundTyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukaemia (CML) show a high success rate. However, low number of patients with long-term treatment-free remission (TFR) is observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24 months with 80% occurrence within the first 6 months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranted new biomarkers for CML. MethodsNext Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at molecular response in CML adult patients receiving TKIs treatment. A total of 86 samples were collected, 30 from CML patients responsive and 28 from non-responsive to imatinib therapy, and 28 from blood donors. NGS was conducted whereby 18 miRNAs were selected and validated by real time RT-qPCR in triplicate. ResultsHsa-miR-181a-5p was expressed significantly (p-value<0.05) with 2.14 and 2.3 fold down-regulation in both patient groups respectively while hsa-miR-182-5p and hsa-miR-26a-5p were significant only in the non-responsive group with 2.08 and 2.39 fold up-regulation respectively. The down-regulation was consistent with decreased amount of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with substantial presence of BCR-ABL1 in CML patients treated with TKIs at molecular response. ConclusionTherefore, these miRNAs have potential as new therapeutic biomarkers for BCR-ABL1 status in adult CML patients treated with TKIs at molecular responses. These could improve current approaches and require further analysis to look for targets of these miRNAs in CML.