Real‐world, multi‐omics validation of the clinical relevance of molecular taxonomy for myelodysplastic syndromes (MDS)

作者：G. Maggioni, G. Todisco, Elisabetta Sauta, L. Lanino, S. Ball, J. Bewersdorf, Tariq Kewan, N. Al Ali, Pierre Fenaux, U. Platzbecker, V. Santini, Zhuoer Xie, Andrew M. Brunner, Andrew T Kuykendall, John M. Bennett, R. Buckstein, R. Bejar, H. Carraway, A. Dezern, E. Griffiths, Stephanie Halene, R. Hasserjian, Alan F. List, S. Loghavi, O. Odenike, Eric Padron, Mrinal M. Patnaik, Gail J Roboz, Maximilian Stahl, M. Sekeres, David P. Steensma, M. Savona, Justin Taylor, Mina L. Xu, D. Sallman, Stephen D. Nimer, Christopher S. Hourigan, Andrew H. Wei, Alessia Campagna, M. Ubezio, E. Riva, Denise Ventura, Nicole Pinocchio, Matteo Zampini, Alessandro Buizza, Antonio Russo, Francesco Pesce, S. D'amico, G. Asti, Mattia Delleani, E. Travaglino, C. Tentori, Ivan Ferrari, Alessandra Crespi, Giulia Figini, M. Di Matteo, Matteo Brindisi, Nicla Manes, Chiara Milanesi, L. Crisafulli, F. Ficara, G. Castellani, U. Borate, F. Efficace, Steven D. Gore, T. K. Kim, M. Díez-Campelo, A. A. van de Loosdrecht, N. Daver, María Rozman, Alberto Orfao, Sa A. Wang, K. Foucar, M. Iastrebner, P. Scheinberg, Yasushi Miyazaki, Y. Madanat, A. Al-Kali, Moshe Mittelmann, T. Cluzeau, L. Adès, Ulrich Germing, G. Garcia-Manero, S. Kordasti, T. Haferlach, A. Zeidan, R. Komrokji, M. G. Della Porta · 发表于：HemaSphere · 年份：2026 · DOI：10.1002/hem3.70406 · 被引用次数：1 · 研究领域：Medicine

Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort (n = 5136) and transcriptomic data from a prospective cohort (n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “TP53‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD3...