HoxBlinc: a key driver of chromatin dynamics in NUP98 fusion–driven leukemia
Jian Xu, Wei Du
Jian Xu, Wei Du
Published April 1, 2025
Citation Information: J Clin Invest. 2025;135(7):e191355. https://doi.org/10.1172/JCI191355.
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HoxBlinc: a key driver of chromatin dynamics in NUP98 fusion–driven leukemia

Abstract

Nucleoporin 98 (NUP98) fusion oncogenes are known to promote aggressive pediatric leukemia by disrupting chromatin structure and modulating the expression of homeobox (HOX) genes, yet the precise molecular events are unclear. In this issue of the JCI, K. Hamamoto et al. explore the mechanistic underpinnings of NUP98 fusion–driven pediatric leukemia, with a focus on aberrant activation of the Hoxb-associated long, noncoding RNA (lncRNA) HoxBlinc. The authors provide compelling evidence that HoxBlinc plays a central role in the oncogenic transformation associated with NUP98 fusion protein. The study underscores a CTCF-independent role of HoxBlinc in the regulation of topologically associated domains (TADs) and chromatin accessibility, which has not been fully appreciated in previous research on the NUP98 fusion oncogenes. The discovery of HoxBlinc lncRNA as a downstream regulator of NUP98 fusion oncoproteins offers a potential target for therapeutic intervention in pediatric leukemia.

Authors

Jian Xu, Wei Du

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Figure 1

HoxBlinc modulates oncogenic transcription and leukemogenesis in NUP98 fusion–driven leukemia.

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HoxBlinc modulates oncogenic transcription and leukemogenesis in NUP98 ...
(A) NUP98 fusion induces aberrant activation of HoxBlinc, causing a reorganization of TADs that alters chromatin interactions. HoxBlinc facilitates chromatin accessibility of MLL1 at promoter regions, ultimately enhancing the expression of HOX and other oncogenic genes. (B) Loss of HoxBlinc reduces MLL1 recruitment and decreases leukemic gene transcription.