c-Myc regulates the CDK1/cyclin B1 dependent‑G2/M cell cycle progression by histone H4 acetylation in Raji cells

Overexpression of c-Myc is involved in the tumorigenesis of B-lineage acute lymphoblastic leukemia (B‑ALL), but the mechanism is not well understood. In the present study, a c‑Myc‑knockdown model (Raji‑KD) was established using Raji cells, and it was indicated that c‑Myc regulates the expression of genes associated with cell cycle progression in G2/M‑phase, cyclin D kinase (CDK)1 and cyclin B1, by modulating 60 kDa Tat‑interactive protein (TIP60)/males absent on the first (MOF)‑mediated histone H4 acetylation (AcH4), which was then completely restored by re‑introduction of the c‑Myc gene into the Raji‑KD cells. The expression of CDK1 and cyclin B1 was markedly suppressed in Raji‑KD cells, resulting in G2/M arrest. In comparison to Raji cells, the proliferation of Raji‑KD cells was significantly reduced, and it was recovered via re‑introduction of the c‑Myc gene. In the tumorigenesis assays, the loss of c‑Myc expression significantly suppressed Raji cell‑derived lymphoblastic tumor formation. Although c‑Myc also promotes Raji cell apoptosis via the caspase‑3‑associated pathway, CDK1/cyclin B1‑dependent‑G2/M cell cycle progression remains the major driving force of c‑Myc‑controlled tumorigenesis. The present results suggested that c‑Myc regulates cyclin B1‑ and CDK1‑dependent G2/M cell cycle progression by TIP60/MOF-mediated AcH4 in Raji cells.