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.

• Klíčová slova
• NGS, bioinformatics, immunophenotyping, microRNA, multiple myeloma,
• MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• mnohočetný myelom * genetika   MeSH
• nádorové mikroprostředí MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH

OBJECTIVES: Progress in multiple myeloma treatment allows patients to achieve deeper responses, for which the assessment of minimal residual disease (MRD) is critical. Typically, bone marrow samples are used for this purpose; however, this approach is site-limited. Liquid biopsy represents a minimally invasive and more comprehensive technique that is not site-limited, but equally challenging. METHODS: While majority of current data comes from short-term studies, we present a long-term study on blood-based MRD monitoring using tumor-specific cell-free DNA detection by ASO-qPCR. One hundred and twelve patients were enrolled into the study, but long-term sampling and analysis were feasible only in 45 patients. RESULTS: We found a significant correlation of quantity of tumor-specific cell-free DNA levels with clinically meaningful events [induction therapy (P = .004); ASCT (P = .012)]. Moreover, length of cfDNA fragments is associated with better treatment response of patients. CONCLUSIONS: These results support the concept of tumor-specific cell-free DNA as a prognostic marker.

• Klíčová slova
• cell-free DNA, liquid biopsy, multiple myeloma, qPCR,
• MeSH
• cirkulující nádorová DNA * MeSH
• hodnocení výsledků zdravotní péče MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• management nemoci MeSH
• mnohočetný myelom diagnóza   genetika   terapie   MeSH
• nádorové biomarkery * MeSH
• polymerázová řetězová reakce MeSH
• průtoková cytometrie MeSH
• reziduální nádor diagnóza   genetika   MeSH
• těžké řetězce imunoglobulinů genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cirkulující nádorová DNA * MeSH
• nádorové biomarkery * MeSH
• těžké řetězce imunoglobulinů MeSH