[MicroRNA Analysis for Extramedullary Multiple Myeloma Relapse]

Multiple myeloma (MM) is the second most common hematooncological disease. Patient survival has been greatly improved by the introduction of new drugs into clinical practice, but survival is negatively affected by the so-called extramedullary relapse (EM), caused by the loss of plasma cell dependence on the bone marrow microenvironment and their migration out of the bone marrow. The nature and causes of this process are currently unclear. MicroRNAs (miRNAs) are short, non-coding RNA molecules involved in many physiological and pathological processes. Their significance in the pathogenesis of MM has been demonstrated by several studies. We assume that they are also involved in the development of the EM. The aim of this study was to analyze different miRNA expression between MM and EM patients.

Using next generation sequencing, we analyzed 39 samples of bone marrow cells from MM patients at diagnosis and 9 bone marrow plasma samples of EM patients.

In total, 2,278 miRNA were sequenced, but only 658 miRNAs were analyzed as they were expressed in all samples and had at least 20 reads. Expression data were generated using the Chimira tool from fastq data. All sequences were mapped using miRBase v20. Further analyses were performed using the R/Bioconductor package. The Bayesian procedure was used for normalization of expression. P values were adjusted using the Benjamini-Hochberg method. Analysis found 10 miRNA (p < 0.0005) that are statistically significantly expressed in EM vs. MM patients - these are miR-26a-5p, miR-26b-5p, miR-30e-5p, miR-424-3p, miR-503-5p, miR-767-5p, miR-105-5p, miR-5695-5p, miR-450b-5p and miR-92b-3p. These miRNAs will be further verified by qPCR method on a larger set of MM and EM patients.

Our pilot study has shown that there are differentially expressed miRNAs between MM and EM patients.Key words: multiple myeloma - microRNA - carcinogenesis - next generation sequencing The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papersThis work was supported by grant MZ ČR AZV 17- 29343A. Submitted: 17. 3. 2018Accepted: 20. 3. 2018.