靶向多瘤病毒相关进行性多灶性白质脑病可根除静止的白血病起始细胞。
PML targeting eradicates quiescent leukaemia-initiating cells.
作者信息
Ito Keisuke, Bernardi Rosa, Morotti Alessandro, Matsuoka Sahoko, Saglio Giuseppe, Ikeda Yasuo, Rosenblatt Jacalyn, Avigan David E, Teruya-Feldstein Julie, Pandolfi Pier Paolo
机构信息
Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
出版信息
Nature. 2008 Jun 19;453(7198):1072-8. doi: 10.1038/nature07016. Epub 2008 May 11.
Abstract
The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.
摘要
在白血病中，已确凿证明存在一小群负责肿瘤维持的“癌症起始细胞”。目前正在实体瘤中验证这一概念。白血病起始细胞，尤其是那些处于静止状态的细胞，被认为对化疗和靶向治疗具有抗性，从而导致疾病复发。慢性粒细胞白血病是一种典型的造血干细胞疾病，其中白血病起始细胞池不会被当前疗法根除，导致停药后疾病复发。在此，我们确定了早幼粒细胞白血病蛋白（PML）肿瘤抑制因子在造血干细胞维持中的关键作用，并提出了一种新的治疗方法，即通过药物抑制PML来靶向静止的白血病起始细胞以及可能的癌症起始细胞。
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