The HELLS-MCM5 axis coordinates transcription-replication dynamics to preserve genomic integrity in ALK-negative anaplastic large cell lymphoma.

HELLS preserves genomic stability and sustains proliferation of ALK-negative anaplastic large cell lymphoma by preventing transcription-replication conflicts through regulation of R-loop homeostasis and MCM5.

• Why it matters: Transcription-replication collisions and R-loop accumulation can destabilize genomes, yet ALK-negative ALCL depends on an oncogenic transcription program that must be coordinated with replication.
• What they did: The study shows HELLS loss lowers MCM5 levels, increases origin firing in transcriptionally active regions, and elevates replication–transcription collisions; HELLS and MCM5 cooperate distally from R-loop-enriched sites.
• The result: Disrupting the HELLS–MCM5 axis increases R-loop burden and drastically reduces ALK-negative ALCL cell survival, supporting combination-therapy rationale targeting this vulnerability.

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