HoxBlinc: a key driver of chromatin dynamics in NUP98 fusion-driven leukemia.

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.