Abstract
Multiple myeloma (MM) is a hematologic malignancy arising from the clonal proliferation of malignant plasma cells. tRNA-derived RNA fragments (tRFs) constitute a class of small non-coding RNAs, deriving from specific enzymatic cleavage of tRNAs. To the best of our knowledge, this is one of few studies to uncover the potential clinical significance of tRFs in MM. Total RNA was extracted from CD138+ plasma cells of MM and smoldering MM patients, and in vitro polyadenylated. First-strand cDNA synthesis was performed, priming from an oligo-dT-adaptor sequence. Next, real-time quantitative PCR (qPCR) assays were developed for the quantification of six tRFs. Biostatistical analysis was performed to assess the results and in silico analysis was conducted to predict the function of one of the tRFs. Our results showed that elevated levels of five out of six tRFs are indicators of favorable prognosis in MM, predicting prolonged overall survival (OS), while two of them constitute potential molecular biomarkers of favorable prognosis in terms of disease progression. Moreover, three tRFs could be used as surrogate prognostic biomarkers along with the R-ISS staging system to predict OS. In conclusion, tRFs show molecular biomarker utility in MM, while their mechanisms of function merit further investigation.
Highlights
Multiple myeloma (MM) is a hematologic malignancy, belonging to a group of disorders characterized as plasma cell dyscrasias, as it emerges from the clonal proliferation of malignant plasma cells
Levels in smoldering MM (sMM) patients’ CD138+ plasma cells, while a mean ± S.E. of 51.5 ± 10.5 relative quantification units (RQUs) was observed for the levels of the same tRNA-derived RNA fragments (tRFs) in MM patients’ CD138+ plasma cells
We showed that 30 -tRF-LeuAAG/TAG was significantly overexpressed in sMM cases compared to MM patients
Summary
Multiple myeloma (MM) is a hematologic malignancy, belonging to a group of disorders characterized as plasma cell dyscrasias, as it emerges from the clonal proliferation of malignant plasma cells. These malignant plasma cells reside in the bone marrow (BM) and, in the majority of cases, synthesize and secrete a monoclonal immunoglobulin (M-protein) [1]. Monoclonal gammopathy of undetermined significance (MGUS) or smoldering MM (sMM), asymptomatic states characterized by clonal proliferation of malignant plasma cells without symptoms, usually precede MM [2,3]. Symptomatic MM is characterized by the presence of end-organ damage, such as hypercalcemia, renal impairment, anemia, and bone disease, as defined by the acronym “CRAB” [4]. MM bone disease (MMBD) is a hallmark of MM, as it degenerates dramatically the quality of life of MM patients [5].
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