Epigenetics as a mechanism of lineage extinction and relapse of B-cell lymphoma treated with CD19 CAR T-cell therapy
Alireza Torabi, Jason Love, David Wu, Alexandre Hirayama, Kikkeri Naresh · 2026
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Description
Alireza Torabi and colleagues write, in a 2026 letter, on DNA changes as a route to relapse after CD19 CAR T-cell therapy for B-cell lymphoma. Resistance often comes through antigen loss, clonal evolution, T-cell exhaustion, or setting change. Antigen loss can follow mutation, splicing, cell nibbling, masking, or DNA silencing. Hypermethylation of the gene promoter can produce antigen-negative relapse while B-cell makeup otherwise stays intact.
Lineage switch, driven by immune pressure, offers an escape: tumors keep clonal relatedness but shift identity and phenotype. The authors reported a relapsed B-cell lymphoma after CAR T therapy with a null phenotype, losing all B-cell markers and CD45, yet expressing CD56 and retaining a BCL2 rearrangement proving its origin. Broad methylation mapping now shows a hypermethylation shift in the relapsed tumor. The authors present DNA reprogramming as the mechanism behind this lineage extinction and relapse.
Catalog record
| CREATOR | Alireza Torabi, Jason Love, David Wu, Alexandre Hirayama, Kikkeri Naresh |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 12 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |