# Not just a by‐product: circular DNA molecules derived from V(D)J recombination are linked to worse prognosis in B‐cell leukemia

## TL;DR

Circular DNA molecules from immune cell development are linked to worse outcomes in B-cell leukemia patients.

## Contribution

The study shows that excised signal circles can replicate and contribute to genome instability in leukemia.

## Key findings

- Excised signal circles (ESCs) can replicate and persist in healthy lymphocytes.
- Higher ESC levels correlate with increased relapse risk in B-cell leukemia patients.
- ESCs may promote genome instability, contributing to leukemia progression.

## Abstract

Excised signal circles (ESC) are circular DNA molecules generated during T‐ and B‐cell maturation. Previously considered biologically inert, recent work by Gao et al. now show that ESCs can replicate and accumulate in healthy lymphocytes. Moreover, the authors link higher levels of ESCs to an increased risk of relapse in B‐cell leukemia patients and propose that this phenomenon is due to the unique ability of ESCs to induce genome instability.

Gao et al. report that circular DNA molecules created as by‐products of V(D)J recombination during lymphocyte maturation (ESCs) can replicate and be retained for much longer than previously thought in healthy cells. In BCP‐ALL cells, increased ESC abundance correlates with a greater chance of relapse likely mediated by their ability to induce genome instability.