Transcriptional repression of CDKN2D by PML/RARα contributes to the altered proliferation and differentiation block of acute promyelocytic leukemia cells

摘要: Cell proliferation and differentiation are highly coordinated processes. These two processes disrupted during leukemogenesis, resulting in block uncontrolled leukemia. To understand the mechanisms disrupting coordination between acute promyelocytic leukemia (APL), we investigated regulatory mechanism of negative cell cycle regulator CDKN2D by leukemia/retinoic acid receptor α (PML/RARα) fusion protein role proliferation. We found that expression APL cells was significantly lower than normal promyelocytes. By chromatin immunoprecipitation luciferase reporter assays, showed PML/RARα directly bound to inhibited transactivation promoter. Further evidence truncated mutated promoters revealed everted repeat 8 (ER8) motif on promoter binding site PML/RARα. Forced induced G0/G1 phase arrest partial granulocytic APL-derived NB4 cells, suggesting function regulating both differentiation. Furthermore, all-trans retinoic (ATRA) knockdown ATRA treatment partially blocked ATRA-induced arrest. Collectively, our data indicate repression disrupts pathogenesis APL, alleviates disruption ensure efficiency. This study provides a for coupling leukemic through action CDKN2D.