Many of the genes with the highest shape disruption (e.g., HHEX, HOXB2, Additional file 1: Fig. S8b) arise early in AML, around the initiation of NPM1 mutation, and subsequently drop to similar expression levels in advanced blasts, highlighting the importance of enriching our data with early leukemic progenitors to detect such initial events. Here, HOXB2 is linked to acute myeloid leukemia.