Molecular-Based Ecosystem to Improve Personalized Medicine in Chronic Myelomonocytic Leukemia

作者：Luca Lanino, Anthony M. Hunter, Nico Gagelmann, M. Robin, Daniele Dall'Olio, Alice Flamigni, Claudia Sala, Carmelo Gurnari, Yu‐Hung Wang, Lisa Pleyer, B. Xicoy, Guillermo Montalban-Bravo, Lee-Yung Shih, Ali Alsugair, Saubia Fathima, Caterina Gregorio, Cesare Rollo, Laura Palomo, Anne Sophie Platzbecker, Gianluca Asti, Raphaël Itzykson, David A. Sallman, Piero Fariselli, Wolfgang Kern, Guillermo Garcia-Manero, U Platzbecker, Francesc Gessé Solé, María Díez-Campelo, Jaroslaw Maciejewski, Rafael Bejar, Felicitas Thol, N. Kroger, Michael R. Savona, Pierre Fenaux, G. F. Sanz, S. Kordasti, Valeria Santini, Michaëla Fontenay, Amer M. Zeidan, Rami S. Komrokji, Torsten Haferlach, Ulrich Germing, Gastone Castellani, Saverio D'Amico, M. Patnaik, F. Ieva, Éric Solary, Ayalew Tefferi, Eric Padron, Matteo Giovanni Della Porta, for the iCPSS Alliance, Tamanna Haque, Omar Abdel-Wahab, Klaus Geissler, Alex Bataller, Alexandre Bazinet, Manja Meggendorfer, Mirco Quintavalla, Alessandro Bruseghini, Elisabetta Sauta, Luciana Carota, Tiziana Sanavia, Lorenzo Dall'Olio, Erica Travaglino, Lurdes López Zamora, David Quintela, Andrés Jerez, Elena Cornejo, Paloma García Martín, Marina Díaz-Beyá, Alejandro Avendano Pita, Verónica Roldán, Dolly Viviana Fiallo Suarez, Estefania Cerezo Velasco, Marisa Calabuig, Esperanza Such, Cristina Castilla-Llorente, Claude Eric Bulabois, Laëtitia Souchet, Hussein Awada, Massimo Bernardi, Patrizia Chiusolo, Antonio Curti, Luisa Giaccone, Carlo Finelli, Ilaria Carola Casetti, Francesco Onida, Lorenza Borin, Matilde Yung Follo, Angela Consagra, Francesco Passamonti, Elisa Diral, Vladan Vucinic, Gregorio Maria Bergonzi, Maria Teresa Voso, Hsin-An Hou, Wen‐Chien Chou, Chi‐Yuan Yao, Chien‐Chin Lin, Hwei‐Fang Tien, Alessia Campagna, Marta Ubezio, Antonio Russo, Gabriele Todisco, Giulia Maggioni, Cristina Astrid Tentori, Alessandro Buizza, Ivan Ferrari, Maria Di Matteo, Alessandra Crespi, Giulia Figini, Camilla Delponte, Francesco Pesce, Matteo Zampini, Elena Riva, Mattia Delleani, Eleonora Iascone, Laura Crisafulli, Francesca Ficara, Denise Ventura, Nicole Pinocchio, Matteo Brindisi, Armando Santoro, Ahmad Kiwan, Jennifer VanOudenhove, Najla H. Al Ali, Timothy A. Graubert, Swapna Thota, Elizabeth A. Griffiths · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-25-02116 · 被引用次数：4 · 研究领域：Acute Myeloid Leukemia Research、Chronic Myeloid Leukemia Treatments、Myeloproliferative Neoplasms: Diagnosis and Treatment

PURPOSE Chronic myelomonocytic leukemia (CMML) is a rare myeloid neoplasm characterized by clinical heterogeneity and is associated with poor outcomes. To date, limited molecular information has been incorporated into disease classification and risk stratification. We aimed to integrate genomic features into the clinical decision-making process for CMML. PATIENTS AND METHODS We analyzed a retrospective cohort of 3013 patients with CMML (training set) and a prospective population of 516 patients (validation set). Using an innovative framework for multimodal data analysis, we developed molecular-based disease taxonomy and prognostication. RESULTS Unsupervised clustering identified nine entities with distinct genomic features and outcomes ( P < .001), including splicing machinery, transcription factors, signal transduction and tyrosine kinase pathways aberrations, and high-risk molecular signatures. Notably, 15% of patients showed molecular/clinical overlap with other myeloid neoplasms. We integrated molecular and clinical information to build the international CMML Prognostic Scoring System (iCPSS), incorporating mutations in nine genes together with hematologic parameters and cytogenetic abnormalities. The iCPSS identified five groups with distinct probability of overall and leukemia-free survival in both training and validation cohorts ( P < .001), outperforming existing prognostic models. Importantly, 55% of patients were reassigned to higher or lower risk groups by th...