Wang Z G, Delva L, Gaboli M, Rivi R, Giorgio M, Cordon-Cardo C, Grosveld F, Pandolfi P P
Department of Human Genetics and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.
Science. 1998 Mar 6;279(5356):1547-51. doi: 10.1126/science.279.5356.1547.
The PML gene is fused to the retinoic acid receptor alpha (RARalpha) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML function was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21WAF1/CIP1 gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARalpha fusion protein may be important in APL pathogenesis.
在与急性早幼粒细胞白血病（APL）相关的染色体易位中，早幼粒细胞白血病（PML）基因与维甲酸受体α（RARα）基因融合。通过同源重组消除小鼠PML蛋白表明，PML调节造血分化并控制细胞生长和肿瘤发生。PML功能对于维甲酸（RA）的肿瘤生长抑制活性及其诱导前体细胞终末髓系分化的能力至关重要。PML是p21WAF1/CIP1基因RA依赖性反式激活所必需的，该基因调节细胞周期进程和细胞分化。这些结果表明，PML是RA途径的关键组成部分，并且PML-RARα融合蛋白对其活性的破坏可能在APL发病机制中起重要作用。
