+1 (202) 780-3397
Hsa-miR-181a-5p, hsa-miR-182-5p and hsa-miR-26a-5p as potential biomarkers for BCR-ABL1 among adult chronic myeloid leukemia treated with tyrosine kinase inhibitors at the molecular response
4th World Congress on SURGICAL PATHOLOGY AND ONCOLOGY RESEARCH
October 17, 2022 | Webinar
Aliza MY, Nor Asiah Muhamad, Kian Meng Chang, Hamidah Akmal Hisham, Yuslina Mat Yusof and Latifah
Ibrahim
Ministry of Health, Malaysia
Posters & Accepted Abstracts : J Clin Path Lab Med
Abstract:
Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. However, a low number of patients with long-term treatment-free remission (TFR) were observed. Molecular relapse after imatinib discontinuation occurred at 50% at 24months, with 80% occurrence within the first 6months. One of the reasons for relapse is untimely TKIs discontinuation caused by large errors from estimates at very low-level or undetectable disease, thus warranting new biomarkers for CML. Methods: Next Generation Sequencing (NGS) was used to identify microRNAs (miRNAs) at the 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. Results Hsa-miR-181a-5p was expressed significantly (p-value< 0.05) with 2.14 and 2.33-fold down-regulation in both patient groups, respectively meanwhile 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. The down-regulation was consistent with decreased amounts of BCR-ABL1 in patients taking TKIs regardless of molecular responses. The up-regulation was consistent with the substantial presence of BCR-ABL1 in CML patients treated with TKIs at the molecular response. Conclusions: Therefore, 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.
References :
1. Alikian M, Gale RP, Apperley JF, Foroni L. Molecular techniques for the personalised management of patients with chronic myeloid leukaemia. Biomol Detect Quantif.
2. Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G. Structural organization of the bcr gene and its role in the Ph’ translocation. Nature.
3. Canaani E, Steiner-Saltz D, Aghai E, Gale RP, Berrebi A, Januszewicz E. Altered transcription of an oncogene in chronic myeloid Leukaemia. Lancet.
PDF HTML