NSD2 E1099K drives relapse in pediatric acute lymphoblastic leukemia by disrupting 3D chromatin organization

The NSD2 p.E1099K (EK) mutation has been shown to be enriched in patients with relapsed ALL indicating a role in clonal evolution and drug resistance. We previously demonstrated that the impact of EK is highly cell context dependent. To uncover 3D chromatin architecture-related mechanisms underlying drug resistance, we performed Hi-C on three B-ALL cell lines heterozygous for NSD2 EK (RS4;11, RCH-ACV, SEM) and assessed changes upon knockdown. We performed Hi-C on three B-ALL cell lines heterozygous for NSD2 EK (RS4;11, RCH-ACV, SEM) and assessed changes upon knockdown for a total of 6 cell lines.