Excised DNA circles from V(D)J recombination promote relapsed leukaemia.

ABSTRACT: Extrachromosomal DNA amplification is associated with poor cancer prognoses¹. Large numbers of excised signal circles (ESCs) are produced as by-products of antigen receptor rearrangement during V(D)J recombination^2,3. However, current dogma states that ESCs are progressively lost through cell division⁴. Here we show that ESCs replicate and persist through many cell generations and share many properties in common with circular extrachromosomal DNAs. Increased ESC copy numbers at diagnosis of B cell precursor acute lymphoblastic leukaemia were highly correlated with subsequent relapse. By taking advantage of the matching recombination footprint that is formed upon the generation of each ESC, we measured ESC persistence and replication and found increased ESC

SUBMITTER: Gao Z 

PROVIDER: S-EPMC12443594 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature