HTLV-1 HBZ inhibits DHX9 to reprogram circRNA biogenesis in ATLL
A virus-driven rearrangement in aggressive T-cell leukemia activates a survival pathway that can be blocked, pinpointing a new therapeutic target for this deadly, understudied cancer.
Comprehensive circRNA profiling across ATLL subtypes reveals extensive remodelling driven by HBZ-mediated inhibition of the DHX9 helicase, which allows intronic RNA duplexes to persist and drives back-splicing of pro-survival circRNAs including circAFF2(3). Silencing circAFF2(3) reduces leukemic cell survival, identifying the HBZ-DHX9-circAFF2(3) axis as a novel post-transcriptional oncogenic mechanism and potential therapeutic target in this highly aggressive and underserved T-cell malignancy.
What the study was
- Study design
- basic_science_mechanistic
- Category
- hematologic_malignancies
- Maturity
- Validated
- Journal
- Tumour Virus Research
Why it surfaced
Novel mechanism of viral oncogene-driven RNA remodelling in ATLL, a rare T-cell leukemia with very poor prognosis and limited treatment options; identifies first HBZ-DHX9 axis. Score 7 (N=3, D=1, P=2, E=1) reflects foundational discovery with unmet need relevance.
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