The genomic and molecular landscape of splenic marginal zone lymphoma, biological and clinical implications.

Autor:	Mirandari A; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK., Parker H; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK., Ashton-Key M; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK.; Department of Pathology, University Hospital Southampton NHS Foundation Trust, SO16 6YD Southampton, UK., Stevens B; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK., Walewska R; Department of Molecular Pathology, University Hospitals Dorset, SO16 6YD Bournemouth, UK., Stamatopoulos K; Institute of Applied Biosciences, Centre for Research and Technology Hellas, 57001 Thessaloniki, Greece., Bryant D; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK., Oscier DG; Department of Molecular Pathology, University Hospitals Dorset, SO16 6YD Bournemouth, UK., Gibson J; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK., Strefford JC; Cancer Sciences, Faculty of Medicine, University of Southampton, SO16 6YD Southampton, UK.
Jazyk:	angličtina
Zdroj:	Exploration of targeted anti-tumor therapy [Explor Target Antitumor Ther] 2024; Vol. 5 (4), pp. 877-901. Date of Electronic Publication: 2024 Jul 23.
DOI:	10.37349/etat.2024.00253
Abstrakt:	Splenic marginal zone lymphoma (SMZL) is a rare, predominantly indolent B-cell lymphoma constituting fewer than 2% of lymphoid neoplasms. However, around 30% of patients have a shorter survival despite currently available treatments and the prognosis is especially poor for the 5-15% of cases that transform to a large cell lymphoma. Mounting evidence suggests that the molecular pathogenesis of SMZL is critically shaped by microenvironmental triggering and cell-intrinsic aberrations. Immunogenetic investigations have revealed biases in the immunoglobulin gene repertoire, indicating a role of antigen selection. Furthermore, cytogenetic studies have identified recurrent chromosomal abnormalities such as deletion of the long arm of chromosome 7, though specific disease-associated genes remain elusive. Our knowledge of SMZL's mutational landscape, based on a limited number of cases, has identified recurring mutations in KLF2 , NOTCH2 , and TP53 , as well as genes clustering within vital B-cell differentiation pathways. These mutations can be clustered within patient subgroups with different patterns of chromosomal lesions, immunogenetic features, transcriptional signatures, immune microenvironments, and clinical outcomes. Regarding SMZL epigenetics, initial DNA methylation profiling has unveiled epigenetically distinct patient subgroups, including one characterized by elevated expression of Polycomb repressor complex 2 (PRC2) components. Furthermore, it has also demonstrated that patients with evidence of high historical cell division, inferred from methylation data, exhibit inferior treatment-free survival. This review provides an overview of our current understanding of SMZL's molecular basis and its implications for patient outcomes. Additionally, it addresses existing knowledge gaps, proposes future research directions, and discusses how a comprehensive molecular understanding of the disease will lead to improved management and treatment choices for patients. Competing Interests: Jonathan C. Strefford is the Editorial Board Member of Exploration of Targeted Anti-tumor Therapy, but he had no involvement in the journal review process of this manuscript. The other authors declare that they have no conflicts of interest. (© The Author(s) 2024.)
Databáze:	MEDLINE
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