BCT-100 induced cell cycle arrest leads to necrotic cell death. (A) Relative expression of cyclins A, B, E in BCT-100–treated AML patient blasts compared with untreated controls (hashed line) were investigated by qPCR. Representative data of 4 patients shown. (B) AML blasts from patients were treated with BCT-100 (600 ng/mL) or cytarabine (500 ng/mL) for 72 hours. Analysis of cell death was performed by transmission electron microscopy. Representative micrographs of 2 of 5 patients shown. Left panel, Untreated cells. Middle panels, Posttreatment with 600 ng/mL BCT-100. Features consistent with organelle enlargement and cell membrane permeabilization. Right panels, Posttreatment with 500 ng/mL cytarabine. Features consistent with nuclear fragmentation bodies and preserved membrane integrity. Experiments performed on 3 separate occasions. (C) Sensitivity to BCT-100 does not correlate with CAT1 expression (D) and only mildly with CAT-2B expression (r = −0.31, P = .41).