Fig 1. CDK inhibitor P1446A induces apoptosis of the CLL B-cells independent of IGHV mutational status and cytogenetics.

(A) PBMC's from patients with CLL (N = 10) were incubated with 0.05–5 μM P1446A or vehicle control for 24 hours and assayed for apoptosis. Here and subsequently, apoptosis was determined by Annexin V staining within the CD19⁺ subset of cells. Horizontal lines represent the mean. (B) CLL B-cells were incubated with 0.05–1.5 μM P1446A for 24 hours. IC₅₀ value was determined for CLL samples with mutated (N = 13) and unmutated IGHV (N = 10). (C) CLL B-cells (N = 62) were incubated with 1.5 μM P1446A for 24 hours. Cytogenetics markers were determined by fluorescent in situ hybridization [no marker, 11q, trisomy 12, 13q, 17p]. Horizontal lines represent the mean. (D) PBMCs from patients with CLL (N = 37) or healthy volunteers (N = 6) were incubated with 1.5 μM P1446A or vehicle control for 24 hours. Since we noted a significant variation in baseline apoptosis between patient samples, normalization to the time-matched untreated controls was performed to more clearly reflect the drug-induced apoptosis. *- p<0.05 compared to untreated control.