Changes in TADs and enhancer hijacking in ALL with 13q12.2 deletion. (A) Juicer KR-normalized Hi‐C interaction heatmaps at 13q12.2 (chr13:28.0 to 29.5 Mb) of the GM12878 cell line, the NALM-6 cell line, and 2 primary high-hyperdiploid ALL cases (25‐kb resolution). The black arrows indicate the TAD boundary between DS1 and DS3 and the red arrow indicates the disruption of this TAD boundary in the case with 13q12.2 deletion (case 3). (B) Insulation score profile at 13q12.2 derived from chromatin interaction sequencing of 6 primary ALL cases. The case with 13q12.2 deletion (case 3) displays a deviant insulation score in this region (blue rectangle), corresponding to aberrant chromatin organization likely due to loss of a TAD boundary. (C) Schematic figure of chromatin remodeling and enhancer hijacking in ALL with 13q12.2 deletion. In normal hematopoietic cells, FLT3 expression is primarily controlled by interactions between the FLT3 promoter element DS1 with the DS2 enhancer located in the 5′ region of PAN3 (top panel). In cells with 13q12.2 deletion, a TAD boundary is lost together with DS2, resulting in increased interactions between DS1 and the upstream enhancer element DS3, thereby upregulating FLT3 messenger RNA expression (bottom panel).