Marginal Zone Lymphoma

AMP-mediated killing, driven by membrane disruption and non-apoptotic death pathways, bypassed conventional resistance mechanisms, suggesting therapeutic potential in relapsed/refractory disease. Our findings highlight natural AMPs as promising candidates for development in drug-resistant MZL, warranting further optimization and preclinical validation.

In this contemporary POL series, clinicopathologic heterogeneity was prominent, and laboratory profiles frequently overlapped with ovarian malignancy work-up. Outcomes may be favorable among patients receiving timely, subtype-appropriate systemic treatment.

P=N/A, N=10, Completed, British Columbia Cancer Agency | Not yet recruiting --> Completed | N=30 --> 10

[68Ga]Ga-PentixaFor PET/CT significantly outperforms [18F]FDG in initial staging of MZL and has a substantial impact on clinical management. Importantly, dual-tracer imaging shows potential as a novel, non-invasive biomarker for in vivo phenotypic characterization, which is associated with early therapeutic outcomes and the identification of high-risk patients.

Case 1 was a 65-year-old woman diagnosed in 2017 with SMZL and treated with rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisone (or prednisolone) (R-CHOP), achieving complete remission, who presented nine years later with recurrent hyperlymphocytosis at 10.8 × 109/L with villous appearance, massive splenomegaly, and systemic symptoms...The patient was treated with rituximab-bendamustine and achieved complete remission...Rituximab monotherapy was followed by rapid improvement, with normalization of the lymphocyte count to 2.13 × 109/L and regression of splenomegaly from the first cycle. These observations highlight the importance of combining lymphocyte immunophenotyping and bone marrow aspiration in isolated splenomegaly with villous lymphocytes on blood smear to avoid underdiagnosis of this new histopathological entity and therefore guide therapeutic management in the absence of guidelines.

P1/2, N=106, Completed, Association International Extranodal Lymphoma Study Group (IELSG) | Active, not recruiting --> Completed

Here, we investigated non-genetic mechanisms of ibrutinib resistance in marginal zone lymphoma (MZL) and their broader therapeutic implications. Pharmacological or genetic disruption of the IL-16/CD9/PI3K axis restored sensitivity to BTK inhibitors and R-CHOP and abrogated IL-16-induced signaling in primary CLL samples. In conclusion, an IL-16/CD9-driven, epigenetically regulated survival pathway represents one possible mechanism of resistance to BTK inhibitors and chemoimmunotherapy, supporting therapeutic targeting of this axis in refractory B-cell lymphomas.

P=N/A, N=25, Not yet recruiting, Sun Yat-sen University

No enriched biological pathways were detected for MZL risk-associated genes. These findings advance our understanding of the genetic architecture of four B-cell lymphoma subtypes and aim to inform future genetic and functional studies.

P=N/A, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University

Multivariate analysis confirmed SMZL-HR as an independent predictor of shorter TTFT (HR: 2.4, p=.001). These findings demonstrate the role of DNA methylation and molecular profiling in SMZL risk stratification.

Together, these results support ionic strength as a key determinant for MALT1 conformational equilibria in solution and suggest how coordinated loop dynamics regulate access to catalytically competent states. This provides a dynamic framework for future structure-based modulation of MALT1 activity.