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Advances in risk stratification enabled the distinction of conventional MCL (cMCL) from non\u2010nodal MCL (nnMCL) subtypes, which presents with distinct biological and clinical features. Prognostic tools such as MIPI\/MIPI\u2010c, Ki\u201067 expression, and <jats:italic>TP53<\/jats:italic> mutation\/deletion status have enhanced risk assessment, while new genomic alterations including 17p deletion, <jats:italic>CDKN2A<\/jats:italic> loss are emerging as a new prognostic factors. Above all, <jats:italic>TP53<\/jats:italic> disruption remains the major adverse factor, associated with poor outcomes despite new combination therapies. Although recent clinical trials are exploring innovative targeted strategies, the effective management of high\u2010risk MCL remains challenging till now. Minimal residual disease (MRD) monitoring is now emerging as a dynamic prognostic tool, offering potential for treatment adaptation. The integration of molecular and clinical predictors into personalized therapeutic strategies along with MRD monitoring could represent the basis of the future algorithm of MCL management.<\/jats:p>","DOI":"10.1002\/hon.70072","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T17:53:41Z","timestamp":1750010021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Advancing Mantle Cell Lymphoma Risk Assessment: Navigating a Moving Target"],"prefix":"10.1002","volume":"43","author":[{"given":"Simone","family":"Ferrero","sequence":"first","affiliation":[{"name":"Hematology Division Department of Molecular Biotechnologies and Health Sciences University of Torino  Torino Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Ragaini","sequence":"additional","affiliation":[{"name":"Hematology Division Department of Molecular Biotechnologies and Health 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