ArticleBlood advances2026
Integrated multiomic profiling reveals 2 distinct splenic marginal zone lymphoma subgroups with prognostic relevance.
Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Advances in targeted and cellular therapies for relapsed/refractory mantle cell lymphoma: immunotherapeutic strategies and challenges.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
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48 authors.
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Abstract
abstractSplenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy with notable genetic, epigenetic, and clinical heterogeneity. In this study, we used coding and noncoding sequencing (n = 74), including whole-genome sequencing (WGS) of 24 paired tumor-normal samples, targeted sequencing (n = 55), and DNA methylation in 126 patients to characterize the disease. From WGS, we identified recurrent, predominantly clonal coding mutations in KLF2 (50%), KMT2D (25%), and NOTCH2 (25%), alongside rare mutations in FLNC (8%), novel mutations in FAM135B (17%), and noncoding mutational hot spots in BCL6, PAX5, and BACH2 linked to aberrant somatic hypermutation. At least 1 noncoding hot spot was detected in 69% of patients. Copy number aberrations were present in 73% of patients, including del(7q) (27%), gain(3q) (17%), and trisomy 12 (13%). DNA methylation profiling revealed 2 epigenetic subgroups: high-risk (HR) SMZL (n = 67) and low-risk SMZL (n = 59). SMZL-HR was associated with adverse features, including female sex, IGHV1-2∗04 usage, KLF2 mutations, del(7q), shorter telomeres, and elevated epigenetically determined cumulative mitoses scores. Transcriptomic analysis highlighted enhanced cell proliferation in SMZL-HR, with enrichment of E2F and G2M checkpoint pathways and epigenetic regulation via EZH2. Patients with SMZL-HR had significantly shorter time to first treatment (TTFT) (hazard ratio, 1.9; P = .003) and reduced overall survival (hazard ratio, 2.5; P = .039): 85% of patients with SMZL-HR required treatment and showed a higher frequency of transformation (P = .007) and mortality (P< .001). Multivariate analysis confirmed SMZL-HR as an independent predictor of shorter TTFT (hazard ratio, 2.4; P = .001). These findings demonstrate the role of DNA methylation and molecular profiling in SMZL risk stratification.
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