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.
Autor: | Mohd Yacob A; Haematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, U13/52 Setia Alam, 40170, Shah Alam, Selangor, Malaysia. aliza.yacob@moh.gov.my., Muhamad NA; Sector for Evidence Based Healthcare, National Institutes of Health, Ministry of Health, Shah Alam, Selangor, Malaysia., Chang KM; Haematology Department, Hospital Ampang, Ministry of Health, Ampang, Selangor, Malaysia., Akmal Hisham H; Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Shah Alam, Selangor, Malaysia., Mat Yusoff Y; Haematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, U13/52 Setia Alam, 40170, Shah Alam, Selangor, Malaysia., Ibrahim L; Special Resource Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Shah Alam, Selangor, Malaysia. |
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Jazyk: | angličtina |
Zdroj: | BMC cancer [BMC Cancer] 2022 Mar 26; Vol. 22 (1), pp. 332. Date of Electronic Publication: 2022 Mar 26. |
DOI: | 10.1186/s12885-022-09396-5 |
Abstrakt: | Background: 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 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 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. (© 2022. The Author(s).) |
Databáze: | MEDLINE |
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