PML targeting eradicates quiescent leukaemia-initiating cells

摘要

The existence of a small population of ‘cancer initiating cells (CICs)’ responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells (LICs), particularly those which are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies resulting in disease relapse. Chronic myeloid leukaemia (CML) is a paradigmatic haematopietic stem cell (HSC) disease in which the LIC pool is not eradicated by current therapy, leading to disease relapse upon drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in HSC maintenance and present a new therapeutic approach for targeting quiescent LICs and possibly CICs by pharmacological inhibition of PML.