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Review
. 2025 Jun;39(6):1337-1341.
doi: 10.1038/s41375-025-02574-x. Epub 2025 Apr 7.

Emerging T-cell lymphomas after CAR T-cell therapy

Till Braun #  1   2 , Florian Kuschel #  3 , Kristin Reiche  4   5   6   7 , Maximilian Merz #  6   7   8   9 , Marco Herling #  7   8
Affiliations
Review

Emerging T-cell lymphomas after CAR T-cell therapy

Till Braun et al. Leukemia. 2025 Jun.
No abstract available

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Conflict of interest statement

Competing interests: MH gave advisory boards and received honoraria from Abbvie, Beigene, Jazz, Janssen, Stemline Menarini, and Takeda, and received research support from EDO-Mundipharma, Janpix, Novartis, and Roche. MM: Advisory Boards/Honoraria/Research support: Amgen, BMS, Celgene, Gilead, Janssen, Stemline, Springworks, and Takeda.

Figures

Fig. 1
Fig. 1. Proposed pathogenetic model of CAR+ T-cell lymphomas.
Suggested trajectories towards CAR+ T-cell lymphoma in the context of pre-existing clonal hematopoiesis of indeterminate potential (CHIP) based on published cases. A mutation in an epigenetic regulator, most commonly TET2 or DNMT3A (yellow asterisk), arises at low frequency in the hematopoietic stem cell compartment. This CHIP-associated alteration leads to a ‘burdened’ myeloid and B-cell lineage, the latter of which potentially even giving rise to the initial B-cell malignancy for which the CAR-T cell therapy was intended. Simultaneously, these precursor lesions can create a permissive T-cell compartment. Following genomic integration of the CAR vector, selective expansion of the mutated T-cell clone occurs, driven by persistent antigenic stimulation, potentially through the CAR’s own target, such as soluble BCMA (sBCMA). The CAR itself thus functions as a continuous signaling driver [24], promoting uncontrolled T-cell proliferation. Additionally, secondary genomic events (red asterisk), such as mutations in JAK or MAPK signaling pathways, further enhance pro-survival and proliferative signaling. Disruptions in DNA damage regulators, exemplified by CHK2, may contribute to genomic instability, facilitating full malignant transformation. To date, genomic CAR integration into a well-established cancer-associated gene has been demonstrated in a single case of CAR+ T-cell lymphoma, in which a monoallelic insertion into the TP53 gene potentially contributed to malignant transformation. Created in BioRender (https://BioRender.com/f50a476).
See this image and copyright information in PMC

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