Nidogen-1, a player in KMT2A rearragned pediatric acute myeloid leukemia

Despite advances in outcome, one third of children with acute myeloid leukemia (AML) relapse, and less than half will achieve long-term survival. Relapse in AML has shown to be driven in part by the leukemic stem cells (LSC), highlighting the unmet medical need to better characterize and target this therapy resistant cell population. Micro-array profiling of pediatric AML subpopulations (LSC and leukemic myelo-blasts) and their healthy counterparts, revealed Nidogen-1 (NID1) as expressed in both leukemic subpopulations, while absent in the hematopoietic stem cell. Using the TAR-GET dataset including pediatric AML patients (n=1025), NID1 expression showed to correlate with worse event-free survival and KMT2A-rearrangements. Drug response profiling of a NID1 knockdown model demonstrated differential sensitivity to HSP90 inhibition. RNA sequencing and gene set enrichment analysis between NID1high and NID1low phenotypes showed involvement of NID1 in mitochondrial metabolic path-ways known to be enriched in the LSC. Altogether, this study highlights NID1 as a novel oncogene associated with worse EFS and metabolic LSC phenotype in AML. NID1 could serve as a biomarker and aid in further mapping LSCs to establish thera-peutic strategies tackling the high relapse rates in pediatric AML.