Overview of the PRECISION-tMN project. The figure illustrates the development of therapyrelated myeloid neoplasms, beginning with cancer onset and exposure to chemotherapy or radiotherapy. Haematopoietic stem cells may acquire age- or treatment-associated mutations (CHIP/ARCH), leading to the emergence of distinct clonal populations. Following treatment exposure, certain clones gain an epigenetic fitness advantage, contributing to disease initiation and progression. The EPI-T-MN research framework integrates multi-omics analyses, patientderived models, and single-cell technologies to dissect these mechanisms. Expected outputs include validated biomarkers, identification of therapeutic targets, establishment of in vitro models, and development of clinical scoring systems, alongside dissemination activities, medical guideline contributions, and intellectual property generation.

PRECISION-tMN aims to revolutionise the clinical management of therapy-related myeloid neoplasms (t-MN) by integrating precision medicine approaches with cutting-edge molecular and computational analyses. t-MN is a serious complication of previous cancer treatments, characterised by poor prognosis and resistance to standard therapies. Despite advances in molecular profiling, the mechanisms driving disease progression and therapeutic resistance remain poorly understood, limiting the development of effective treatment strategies.

This consortium brings together a multidisciplinary and transnational collaboration to investigate the interplay between genetic mutations, epigenetic modifications, transcriptional alterations, and immune dysregulation in t-MN. By combining multi-omics approaches (genomics, epigenomics, and transcriptomics) with advanced bioinformatics, artificial intelligence, and clinical data, the project aims to identify pharmacogenomic biomarkers for risk stratification and therapeutic targeting. State-of-the-art patient-derived models and single-cell technologies will be used to explore disease heterogeneity and responses to treatment.

PRECISION-tMN unites leading academic institutions, hospitals, and patient associations, ensuring access to large patient cohorts, high-quality biobanks, standardised diagnostic platforms, and extensive existing datasets. This collaborative effort will validate novel therapeutic targets and accelerate their translation into clinical practice, ultimately paving the way for personalised treatment strategies. The project will also support data harmonisation, knowledge dissemination, and training initiatives, fostering long-term progress in precision oncology for t-MN.