Analysis of BCR-ABL1–induced leukemogenesis. (A) [³H]-thymidine incorporation in low-serum cultures of bone marrow–derived p185^BCR-ABL-transformed cells (mean ± standard deviation [SD]; n = 4 clones, Cdk4^R/R; Cdk6^R/R and n = 3 clones, all other genotypes; 1-way ANOVA including Bonferroni’s multiple comparison test). (B) Survival of NSG mice after intravenous injection of p185^BCR-ABL–transformed cell lines. Data from 3 independent experiments are presented; log-rank test). (C) Analysis of the cell-cycle profile in the absence or presence of 255 nM PD-0332991 (mean ± SD; n = 4 clones for all genotypes). (D) Dose response curves for PD-0332991 after 48 hours’ treatment (mean ± SD; n = 4 clones for all genotypes). (E) A summary of transcripts up- (red) or down- (green) regulated (fold-change >2) in Cdk4^R/R; Cdk6^R/R compared with wild-type clones (n = 3 clones per genotype). (F) Transcripts deregulated in BCR-ABL1–transformed Cdk4^R/R; Cdk6^R/R cells displayed promoter sequences significantly enriched compared with BCR-ABL1–transformed wild-type cultures) in recognition sites for the indicated transcription factors. (G) Validation of the differential expression of specific proteins, predicted in the microarray analysis, using immunoblot (p65 NF-kB, IGF-1 Traf2) or flow cytometry (interleukin-2Ra [IL-2Ra]) analysis using 4 individual cell clones per genotype; 1-way ANOVA including Bonferroni’s multiple comparison test; *P < .05; **P < .01).