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. 2025 Sep 25;13(10):2347.
doi: 10.3390/biomedicines13102347.

Impact of KMT2A Rearrangement on Peripheral T-Cell Lymphoma, Not Otherwise Specified, and Angioimmunoblastic T-Cell Lymphoma

Tong-Yoon Kim  1   2 , Tae-Jung Kim  3 , Eun Ji Han  4 , Gi-June Min  2   5 , Seok-Goo Cho  2   5 , Youngwoo Jeon  1   2
Affiliations

Impact of KMT2A Rearrangement on Peripheral T-Cell Lymphoma, Not Otherwise Specified, and Angioimmunoblastic T-Cell Lymphoma

Tong-Yoon Kim et al. Biomedicines. .

Abstract

Background: Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL), not otherwise specified (NOS), share overlapping histology and T-follicular helper (TFH) biology but often show divergent outcomes and treatment needs. The clinical significance of KMT2A rearrangement (KMT2A-r) in nodal PTCL remains undefined. We aimed to investigate the clinicogenomic features and prognostic impact of KMT2A-r in AITL and PTCL-NOS. Methods: We retrospectively analyzed consecutive patients diagnosed with AITL or PTCL-NOS between 2021 and 2024 at two centers. All patients underwent 523-gene DNA/RNA next-generation sequencing. Gene co-variation and diagnostic splits were summarized using network and decision-tree analyses. Results: Overall, 37 patients were included (AITL: 14; PTCL-NOS: 23), with similar baseline clinical characteristics. In AITL, TFH markers were more frequently expressed, and RHOA mutations were enriched. KMT2A-r occurred in 24% of cases without histology-specific enrichment. AITL showed better 2-year overall survival (OS) than PTCL-NOS (70.7% vs. 38.8%; p = 0.040) but similar progression-free survival (PFS). Univariate analysis revealed that KMT2A-r, lactate dehydrogenase elevation, and bone-marrow involvement predicted inferior PFS (Hazard ratio for KMT2A-r: 2.56). Median PFS was 5.9 versus 12.5 months in the KMT2A-r and non-KMT2A-r groups, respectively (p = 0.039). Brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone did not significantly improve OS or PFS overall; however, exploratory analysis indicated improved PFS in the KMT2A-r subset. Conclusions: KMT2A-r delineates an adverse-risk biology in nodal PTCL, aligns with non-TFH genomic hubs and markers of tumor burden, and may serve as a stratifier and hypothesis-generating target for BV-based strategies.

Keywords: Angioimmunoblastic T-cell lymphoma; KMT2A rearrangement; non-Hodgkin lymphomas; peripheral T-cell lymphoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Survival according to histology and initial regimen. Kaplan–Meier curves for OS and PFS by (A,B) histology (AITL vs. PTCL-NOS), (C,D) initial regimen (BV-CHP vs. non-BV-CHP) Tick marks denote censoring; numbers at risk are shown below the axes.
Figure 2
Figure 2
Genomic landscape and outcome by KMT2A rearrangement (KMT2A-r). (A) Oncoprint summarizing alteration frequencies (rows) across cases (columns), colored based on histology. (B) OS by KMT2A-r (positive vs. negative). (C) PFS by regimen (BV-CHP vs. non-BV-CHP) in KMT2A-r positive group. neg, negative; pos, positive.
Figure 3
Figure 3
Clinicogenomic map (A) Correlation heatmap across clinical and genomic features. Tiles encode Pearson’s r (color scale). Cells not reaching two-sided p < 0.05 are marked with a cross (×); symbols are displayed on the lower triangle only to avoid duplication. (B) Gene co-variation network with betweenness highlighting (Top vs. Rest) (C) rpart decision tree separating AITL vs. PTCL using binary features (1 = present).
See this image and copyright information in PMC

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