Induced HMGA2 expression sensitizes leukemic cells to ATR, CHK1, and PLK1 inhibitors . HMGA2 protein expression (A), proliferation curves (B), and cell cycle analysis (C) were performed in K562 cells infected with control YFP– or HMGA2-YFP–expressing vectors. (D) Dose-response curves and IC₅₀ values for representative ATR, CHK1 and ATR/DNA-PK/mTOR inhibitors in K562 cells infected with vectors expressing control YFP (blue) or HMGA2-YFP (red). (E) Representation of overall chemical screen results in primary AML and cell lines (K562, OCI-AML5, and THP-1). Compounds with a significant increased activity in CK HMGA2⁺ vs CK HMGA2^– primary AML (see Figure 4E) are depicted in orange while nonsignificant compounds are in blue. In cell lines, compounds with more than a twofold decrease in IC₅₀ values in HMGA2-expressing cells vs control are in red; others are in blue. Fold change in IC₅₀ values are indicated in corresponding boxes. (F) PLK1 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). Dose-response curves and IC₅₀ values for volasertib and GSK46136 PLK1 inhibitors in K562 (G) and THP-1 (H) cells infected with vectors expressing control YFP (blue) or HMGA2-YFP (red). mTOR, mammalian target of rapamycin; PARP, poly(ADP-ribose) polymerase.