Extramedullary multiple myeloma (EMD) is an aggressive disease; malignant plasma cells lose their dependence in the bone marrow microenvironment and migrate into tissues. EMD is a negative prognostic factor of survival. Using flow cytometry and next-generation sequencing, we aimed to identify antigens and microRNAs (miRNAs) involved in EMD pathogenesis. Flow cytometry analysis revealed significant differences in the level of clonal plasma cells between MM and EMD patients, while the expression of CD markers was comparable between these two groups. Further, miR-26a-5p and miR-30e-5p were found to be significantly down-regulated in EMD compared to MM. Based on the expression of miR-26a-5p, we were able to distinguish these two groups of patients with high sensitivity and specificity. In addition, the involvement of deregulated miRNAs in cell cycle regulation, ubiquitin-mediated proteolysis and signaling pathways associated with infections or neurological disorders was observed using GO and KEGG pathways enrichment analysis. Subsequently, a correlation between the expression of analyzed miRNAs and the levels of CD molecules was observed. Finally, clinicopathological characteristics as well as CD antigens associated with the prognosis of MM and EMD patients were identified. Altogether, we identified several molecules possibly involved in the transformation of MM into EMD.

Babak Myeloma Group Department of Pathophysiology Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Centre for Molecular Medicine Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic

Department of Clinical Hematology University Hospital Brno 625 00 Brno Czech Republic

Department of Hemato Oncology University Hospital Olomouc and Faculty of Medicine and Dentistry Palacky University Olomouc 779 00 Olomouc Czech Republic

Department of Hematooncology University Hospital Ostrava Ostrava and Faculty of Medicine University Ostrava 708 00 Ostrava Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno 625 00 Brno Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

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Detection of early relapse in multiple myeloma patients

MicroRNA Profiling of Bone Marrow Plasma Extracellular Vesicles in Multiple Myeloma, Extramedullary Disease, and Plasma Cell Leukemia