Increased sensitivity of HMGA2⁺ primary AMLs toward G2/M checkpoint inhibitors. (A) List of inhibitors and their primary target(s) used in the chemical screen. Genotoxic agents used as controls are not listed. (B) Repartition of the primary AML specimens selected and screen layout. Volcano plot showing the differential compound sensitivity in CK vs intermediate-risk AML specimens (C), TP53 wild-type (WT) vs TP53 altered AML samples (D), and CK HMGA2^– vs CK HMGA2⁺ samples (E). White dots represent genotoxic agents. (F) Dot plot comparison of representative ATR, CHK1, and WEE1 inhibitors between intermediate, CK HMGA2^–, and CK HMGA2⁺ specimens (median is depicted, Mann-Whitney U test). (G) CHEK1, WEE1, ATM, and CHEK2 messenger RNA expression in HMGA2 null (RPKM = 0; n = 83) and HMGA2 high (RPKM >2; n = 39) AML samples (median is depicted, Mann-Whitney U test). 5-FU, 5-fluorouracil; ns, not significant; PARP, poly(ADP-ribose) polymerase.