Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine Bronx, NY, USA ; Department of Cell Biology, Albert Einstein College of Medicine Bronx, NY, USA ; Department of Medicine, Albert Einstein College of Medicine Bronx, NY, USA ; Albert Einstein Cancer Center, Albert Einstein College of Medicine Bronx, NY, USA.
Front Oncol. 2013 Mar 14;3:50. doi: 10.3389/fonc.2013.00050. eCollection 2013.
It has long been believed that the tumor suppressor promyelocytic leukemia (PML), the core component of the nuclear substructures known as the PML-nuclear bodies, plays a key part in acute PML (APL), as it is first cloned at the breakpoint of the t(15;17) translocation typical of that disease. Research over the past decade, however, has radically changed our view of how this tumor suppressor is regulated, how it can be therapeutically targeted, and how it functions in a number of tissue systems. One noteworthy recent study, for instance, revealed that PML regulates the activation of fatty acid metabolism, and that this metabolic reprograming plays an essential role in cancer biology and stem cell biology through the control it exerts over stem cell fate decisions. These findings sparked exciting new investigations of PML as a critical "rheostat" responsible for fine-tuning tissue homeostasis, and thus created at the intersection of cancer and stem cell biology a new field of study with important therapeutic implications.
长期以来,人们一直认为肿瘤抑制因子早幼粒细胞白血病(PML)是核亚结构的核心组成部分,这些核亚结构被称为 PML 核体,在急性早幼粒细胞白血病(APL)中起着关键作用,因为它是首先在该疾病典型的 t(15;17)易位断点处被克隆的。然而,过去十年的研究极大地改变了我们对这种肿瘤抑制因子如何被调节、如何进行治疗性靶向以及在许多组织系统中发挥功能的看法。例如,最近的一项值得注意的研究表明,PML 调节脂肪酸代谢的激活,并且这种代谢重编程通过控制干细胞命运决定,在癌症生物学和干细胞生物学中发挥着至关重要的作用。这些发现激发了人们对 PML 作为负责微调组织平衡的关键“变阻器”的新的研究,从而在癌症和干细胞生物学的交叉点上产生了一个具有重要治疗意义的新研究领域。