miR-486-5p: A Prognostic Biomarker for Chronic Myeloid Leukemia

Anupama Ninawe; Sameer Ahmad Guru; Prasant Yadav; Mirza Masroor; Amit Samadhiya; Namrata Bhutani; Naresh Gupta; Richa Gupta; Alpana Saxena

doi:10.1021/acsomega.1c00035

miR-486-5p: A Prognostic Biomarker for Chronic Myeloid Leukemia

ACS Omega. 2021 Mar 15;6(11):7711-7718. doi: 10.1021/acsomega.1c00035. eCollection 2021 Mar 23.

Authors

Anupama Ninawe¹, Sameer Ahmad Guru¹, Prasant Yadav¹, Mirza Masroor¹, Amit Samadhiya¹, Namrata Bhutani¹, Naresh Gupta², Richa Gupta³, Alpana Saxena¹

Affiliations

¹ Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, India.
² Department of Medicine, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, India.
³ Department of Pathology, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, India.

Abstract

MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a therapeutic target in various cancers. In this study, we analyzed alterations in the expression of miR-486-5p in chronic Myeloid Leukemia (CML) patients. Initially, the expression of miR-486-5p was studied in the BCR-ABL1+ve CML K562 cell line by quantitative real-time polymerase chain reaction (qRT-PCR). The results indicated that the miR-486-5p expression was significantly upregulated in K562 cells after imatinib exposure, as compared to untreated K562 cells (p-value = 0.047). These observations were corroborated by a hospital-based study of the miR-486-5p expression in peripheral blood leucocytes of 36 CML patients in the chronic phase (CP) and compared with age and sex-matched healthy volunteers as control subjects. qRT-PCR-based quantification revealed significant downregulation of the miR-486-5p expression in newly diagnosed untreated CP-CML patients' samples (2^-ΔCt = 13.19 ± 14.41) as compared to control samples (2^-ΔCt = 254.5 ± 274.8) (p-value < 0.0001). Levels of miR-486-5p were found to be distinctly elevated in the post-imatinib treatment samples of CML patients (2^-ΔCt = 469.7 ± 312.9) as compared to pre-treatment samples (p-value < 0.0001). CML patients' clinical and hematological responses to imatinib therapy (oral dose of 400 mg OD) were monitored for 12 months. The correlation of pre-treatment miR-486-5p levels with Sokal score indicated that patients with a higher expression of miR-486-5p had better prognoses. Patients with higher pre-imatinib miR-486-5p levels also showed a major hematologic response to imatinib in a shorter time and vice versa. To the best of our knowledge, this is the first report of alterations in the miR-486-5p expression in peripheral blood leucocytes of CML patients. Our observations support a tumor suppressor role of miR-486-5p in CML. The downregulation of the miR-486-5p expression may be critically important in the disease progression of CML patients. The upregulation of the miR-486-5p expression in post-imatinib exposure K562 cells and CML patients after 12 months of imatinib treatment suggests an onco-suppressor effector role of miR-486-5p in the BCR-ABL downstream signaling pathway. miR-486-5p can be explored as a novel biomarker for the early detection of CML.