4.8 Article

PML targeting eradicates quiescent leukaemia-initiating cells

Journal

NATURE
Volume 453, Issue 7198, Pages 1072-U4

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nature07016

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Funding

  1. NCI NIH HHS [R37 CA071692, R00 CA139009, K99 CA139009, R37 CA071692-12] Funding Source: Medline

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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.

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