miR-638 in circulating leukaemia cells as a non-invasive biomarker in diagnosis, treatment response and MRD surveillance of acute promyelocytic leukaemia

Article type: Research Article

Authors: Bai, Yuanyuan^{a; 1} | Chen, Cheng^{b; 1} | Guo, Xiaoling^c | Ding, Ting^{a; d} | Yang, Xinyun^{a; d} | Yu, Jian^a | Yang, Junjun^a | Ruan, Jichen^e | Zheng, Xiaoqun^{a; *} | Chen, Zhanguo^{a; *}

Affiliations: [a] Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China | [b] Department of Hematology, Wenzhou Key Laboratory of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China | [c] Center of Scientific Research, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China | [d] The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China | [e] Department of Pediatric Hematology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

Correspondence: [*] Corresponding authors: Xiaoqun Zheng and Zhanguo Chen, Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325000, China. E-mails: [email protected] and [email protected].

Note: [1] These authors contributed equally.

Abstract: BACKGROUND: MicroRNA (miRNA) expression has been implicated in leukaemia. In recent years, miRNAs have been under investigation for their potential as non-invasive biomarkers in acute promyelocytic leukaemia (APL). We investigated whether miR-638 in circulating leukaemia cells is a non-invasive biomarker in diagnosis, assessment of the treatment response and minimal residual disease (MRD) surveillance of APL. METHODS: Sixty cases of acute myeloid leukaemia (AML), including 30 cases of APL and 30 cases of non-APL AML, were selected. Thirty healthy controls were also selected. Bone marrow (BM) and peripheral blood (PB) samples were collected from APL patients at diagnosis and post-induction. Microarray analysis and quantitative real-time PCR (qRT-PCR) were performed for miRNA profiling and miR-638 expression analysis, respectively. For statistical analysis, Mann-Whitney U test, Wilcoxon Signed Rank test, receiver operating characteristic (ROC) curve analysis and Spearman’s rho correlation test were used. RESULTS: Both microarray and qRT-PCR data showed that miR-638 was significantly upregulated in BM after APL patients received induction therapy. Moreover, miR-638, which is specifically downregulated in APL cell lines, was upregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation. Receiver operating characteristic (ROC) curve analyses revealed that miR-638 could serve as a valuable biomarker for differentiating APL from controls or non-APL AML. Furthermore, miR-638 expression was sharply increased after induction therapy and complete remission (CR). An inverse correlation was observed between miR-638 and PML-RARα transcripts levels in BM samples, while a positive correlation was revealed between PB miR-638 and BM miR-638 levels in APL patients after induction therapy. CONCLUSIONS: Our study suggested that miR-638 may serve as a potential APL biomarker for diagnosis and assessment of the response to targeted therapy, and PB miR-638 could be used for non-invasive MRD surveillance in APL.

Keywords: Acute promyelocytic leukaemia, miR-638, non-invasive biomarker, treatment response, minimal residual disease

DOI: 10.3233/CBM-190899

Journal: Cancer Biomarkers, vol. 29, no. 1, pp. 125-137, 2020