NSD2 E1099K Drives Relapse in Pediatric Acute Lymphoblastic Leukemia by Disrupting 3D Chromatin Organization

NSD2 p.E1099K (EK) is a mutation shown to be enriched in patients that relapse with pediatric Acute Lymphoblastic Leukemia (ALL). This work aims to uncover 3D chromatin architecture-related mechanisms responsible for drug resistance or therapy failure in these patients. We investigated this by performing Hi-C, ATAC-Seq, and RNA-Seq on three B-ALL cell lines heterozygous for EK either expressing a NSD2 targeting small RNA (sRNA) or a non-targeting small hairpin RNAs (shRNA). We also performed RNA-Seq on three matched diagnosis/relapse B-ALL samples with the relapse enriched EK mutation. ]]>
We included specifically matched diagnosis/relapse patient pairs that presented with the relapse enriched NSD2 p.E1099K mutation.]]>
The patient samples included in this study were part of the Phase III clinical trial AALL1331: Risk-Stratified Randomized Phase III Testing of Blinatumomab in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL). AALL1331 was opened on December 8, 2014. RNA-Seq data from these samples was generated by St. Jude Children's Research Hospital, Computational Biology Genomics Laboratory. ]]>