KEY TAKEAWAYS
- The study aimed to investigate the molecular mechanisms underlying HT in MZLs to improve understanding and treatment strategies.
- Researchers noticed that distinct clinicopathologic and genetic features of HT-MZLs suggest a unique entity, potentially differentiated from MZL and de novo non-GCB type DLBCL, with TBL1XR1 mutations as a predictive marker.
Marginal zone lymphomas (MZLs) are a heterogeneous group of slow-growing lymphoproliferative disorders. However, a subset of patients experiences histologic transformation (HT), leading to rapid progression to aggressive lymphoma.
Anqi Li and the team aimed to investigate the role of TBL1XR1 mutations as a potential predictor of HT in MZL.
Researchers performed an inclusive analysis involving 43 MZLs with histologic transformation (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without MYC, BCL2, and BCL6 rearrangements. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs underwent 148-gene targeted exome sequencing. The study compared clinicopathologic features and genetic alterations in patients with HT-MZL, MZLs, and DLBCLs.
About the study’s results, all 43 HT-MZL cases corresponded to DLBCLs, with none harboring BCL2 and MYC and/or BCL6 rearrangements. HT-MZLs exhibited higher rates of bone marrow involvement and elevated lactate dehydrogenase levels compared to MZLs. Upregulated expression of BCL6, MUM1, C-MYC, and Ki-67 was more common in HT-MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%).
Patients with TBL1XR1 mutations showed a trend toward worse progression-free survival. Additionally, HT-MZLs displayed significantly higher frequencies of TBL1XR1 and ID3 mutations compared to MZLs and non-germinal center B-cell (GCB) type DLBCLs. PIM1 mutations, which were frequently observed in DLBCLs, showed a significant association with TBL1XR1 mutations but were less common in HT-MZLs with TBL1XR1 mutations.
The study concluded that the clinicopathologic and genetic characteristics of HT-MZLs suggest their potential differentiation from both MZL and de novo non-germinal center B-cell (GCB) type DLBCL. Notably, TBL1XR1 mutations emerged as potential predictors of histologic transformation in MZL.
The study was sponsored by the National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality.
Source: https://pubmed.ncbi.nlm.nih.gov/37941429/
Li A, Yi H, Deng S, et al. (2024). “The genetic landscape of histologically transformed marginal zone lymphomas.” Cancer. 2024 Apr 15;130(8):1246-1256. doi: 10.1002/cncr.35072. Epub 2023 Nov 8. PMID: 37941429.
