@article {44682,
	title = {Small RNA-seq and clinical evaluation of tRNA-derived fragments in multiple myeloma: Loss of mitochondrial i-tRF(HisGTG) results in patients{\textquoteright} poor treatment outcome},
	journal = {British Journal of Haematology},
	volume = {204},
	number = {5},
	year = {2024},
	note = {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.},
	month = {May},
	pages = {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{\textquoteright} 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{\textquoteright} clinical data (HR = 1.954; p = 0.036). Additionally, mt-i-tRF(HisGTG)-fitted multivariate models led to superior risk stratification of MM patients{\textquoteright} 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{\textquoteright} treatment outcome.},
	keywords = {*Multiple Myeloma/genetics/mortality/pathology, Adult, Aged, Aged, 80 and over, CD138+ plasma cells, Female, haematological cancer, Humans, internal tRFs, Male, Middle Aged, Mitochondria/genetics, mitochondrial tRFs, Molecular markers, non-coding RNAs, Prognosis, RNA, Transfer/genetics, RNA-Seq, Small RNA-seq, Treatment Outcome, tRF-seq, tRFs, tRNA-derived fragments, tRNA-derived small RNA fragments, tsRNAs},
	isbn = {1365-2141 (Electronic)0007-1048 (Linking)},
	author = {Soureas, K. and Papadimitriou, M. A. and Malandrakis, P. and Papanota, A. M. and Adamopoulos, P.G. and Ntanasis-Stathopoulos, I. and Liacos, C. I. and Gavriatopoulou, M. and Sideris, D. C. and Kastritis, E. and Dimopoulos, M.A. and Scorilas, A. and Terpos, E. and Avgeris, M.}
}
