@article {44676,
	title = {Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome},
	journal = {Blood Cancer Journal},
	volume = {15},
	number = {1},
	year = {2025},
	note = {Soureas, KonstantinosMalandrakis, PanagiotisPapadimitriou, Maria-AlexandraMinopoulos, ChristosNtanasis-Stathopoulos, IoannisLiacos, Christine-IvyGavriatopoulou, MariaKastritis, EfstathiosDimopoulos, Meletios-AthanasiosScorilas, AndreasAvgeris, MargaritisTerpos, EvangelosengProject 101097094/European Commission (EC)/Research Support, Non-U.S. Gov{\textquoteright}t2025/03/16 12:43Blood Cancer J. 2025 Mar 15;15(1):41. doi: 10.1038/s41408-025-01248-2.},
	month = {Mar 15},
	pages = {41},
	abstract = {The persistence of high relapse rates and therapy resistance continues to challenge the effective management of multiple myeloma (MM). The identification of novel MM-specific molecular markers could ameliorate risk-stratification tools and accurately identify high-risk patients towards personalized prognosis and therapy. miRNA-seq analysis of CD138+ plasma cells (n = 24) unveiled miR-221-3p and miR-222-3p (miR-221/222 cluster) as the most downregulated miRNAs in R-ISS III compared to R-ISS I/II patients. Subsequently, miR-221/222 levels were quantified by RT-qPCR in CD138+ plasma cells of our screening cohort (n = 141), assessing patients{\textquoteright} mortality and disease progression as clinical endpoints. Internal validation was performed by bootstrap analysis, while clinical benefit was estimated by decision curve analysis. Kryukov et al. (n = 149) and Aass et al. (n = 86) served as institutional-independent validation cohorts. Loss of miR-221/222 cluster was strongly associated with patients{\textquoteright} short-term progression and poor overall survival, which was confirmed by Kryukov et al. and Aass et al. validation cohorts. Intriguingly, miR-221/222-fitted multivariate models offered superior risk-stratification within R-ISS staging and risk-based cytogenetics. Moreover, miR-221/222 loss could effectively discriminate optimal 1st-line treatment responders with inferior treatment outcome. Our study identified the loss of miR-221/222 cluster as a powerful independent predictor of patients{\textquoteright} post-treatment progression, ameliorating prognosis and supporting precision medicine in MM.},
	keywords = {*MicroRNAs/genetics, *Multiple Myeloma/genetics/mortality/pathology/therapy/diagnosis, *Plasma Cells/metabolism/pathology, *Syndecan-1/metabolism, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/genetics, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Prognosis, Treatment Outcome},
	isbn = {2044-5385 (Electronic)2044-5385 (Linking)},
	author = {Soureas, K. and Malandrakis, P. and Papadimitriou, M. A. and Minopoulos, C. and Ntanasis-Stathopoulos, I. and Liacos, C. I. and Gavriatopoulou, M. and Kastritis, E. and Dimopoulos, M.A. and Scorilas, A. and Avgeris, M. and Terpos, E.}
}
