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Small RNA-seq and clinical evaluation of tRNA-derived fragments in multiple myeloma: Loss of mitochondrial i-tRF(HisGTG) results in patients' poor treatment outcome

Citation:

Soureas K, Papadimitriou MA, Malandrakis P, Papanota AM, Adamopoulos PG, Ntanasis-Stathopoulos I, Liacos CI, Gavriatopoulou M, Sideris DC, Kastritis E, Dimopoulos MA, Scorilas A, Terpos E, Avgeris M. Small RNA-seq and clinical evaluation of tRNA-derived fragments in multiple myeloma: Loss of mitochondrial i-tRF(HisGTG) results in patients' poor treatment outcome. British Journal of Haematology 2024;204:1790-1800.

Abstract:

Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA-derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM-related tRFs in ameliorating MM prognosis and risk stratification. Small RNA-seq was performed to profile tRFs in bone marrow CD138(+) plasma cells, revealing the significant deregulation of the mitochondrial internal tRF(HisGTG) (mt-i-tRF(HisGTG)) in MM versus sMM/MGUS. The screening cohort of the study consisted of 147 MM patients, and mt-i-tRF(HisGTG) levels were quantified by RT-qPCR. Disease progression was assessed as clinical end-point for survival analysis, while internal validation was performed by bootstrap and decision curve analyses. Screening cohort analysis highlighted the potent association of reduced mt-i-tRF(HisGTG) levels with patients' bone disease (p = 0.010), osteolysis (p = 0.023) and with significantly higher risk for short-term disease progression following first-line chemotherapy, independently of patients' clinical data (HR = 1.954; p = 0.036). Additionally, mt-i-tRF(HisGTG)-fitted multivariate models led to superior risk stratification of MM patients' treatment outcome and prognosis compared to disease-established markers. Notably, our study highlighted mt-i-tRF(HisGTG) loss as a powerful independent indicator of post-treatment progression of MM patients, leading to superior risk stratification of patients' treatment outcome.

Notes:

Soureas, KonstantinosPapadimitriou, Maria-AlexandraMalandrakis, PanagiotisPapanota, Aristea-MariaAdamopoulos, Panagiotis GNtanasis-Stathopoulos, IoannisLiacos, Christine-IvyGavriatopoulou, MariaSideris, Diamantis CKastritis, EfstathiosDimopoulos, Meletios-AthanasiosScorilas, AndreasTerpos, EvangelosAvgeris, Margaritiseng101097094/European Union/England2024/02/28 06:45Br J Haematol. 2024 May;204(5):1790-1800. doi: 10.1111/bjh.19332. Epub 2024 Feb 27.