Aitken Marisa J L, Lee Hun J, Post Sean M
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Lymphoma and Multiple Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ther Adv Hematol. 2019 Dec 5;10:2040620719891356. doi: 10.1177/2040620719891356. eCollection 2019.
Over the past 40 years, p53 has been the most widely studied protein in cancer biology. Originally thought to be an oncogene due to its stabilization in many cancers, it is now considered to be one of the most critical tumor suppressors in a cell's ability to combat neoplastic transformation. Due to its critical roles in apoptosis, cell-cycle arrest, and senescence, deletions and mutations are commonly observed and are often a portent of treatment failures and poor clinical outcomes. This is particularly true in chronic lymphocytic leukemia (CLL), as patients with p53 alterations have historically had dismal outcomes. As such, the tremendous efforts made to better understand the functions of p53 in CLL have contributed substantially to recent advances in treating patients with p53-pathway-deficient CLL.
在过去40年里,p53一直是癌症生物学领域研究最为广泛的蛋白质。由于其在许多癌症中表现出稳定性,最初被认为是一种癌基因,如今则被视为细胞对抗肿瘤转化能力中最关键的肿瘤抑制因子之一。因其在细胞凋亡、细胞周期阻滞和衰老过程中发挥着关键作用,所以常见p53基因缺失和突变,而这往往预示着治疗失败和临床预后不佳。在慢性淋巴细胞白血病(CLL)中尤其如此,因为历史上p53基因发生改变的患者预后都很糟糕。因此,为更好地理解p53在CLL中的功能所付出的巨大努力,极大地推动了近期针对p53通路缺陷型CLL患者治疗的进展。