PML targeting eradicates quiescent leukaemia-initiating cells

Keisuke Ito, Rosa Bernardi, Alessandro Morotti, Sahoko Matsuoka, Giuseppe Saglio, Yasuo Ikeda, Jacalyn Rosenblatt, David E. Avigan, Julie Teruya-Feldstein, Pier Paolo Pandolfi

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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.

Original languageEnglish (US)
Pages (from-to)1072-1078
Number of pages7
JournalNature
Volume453
Issue number7198
DOIs
StatePublished - Jun 19 2008

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Ito, K., Bernardi, R., Morotti, A., Matsuoka, S., Saglio, G., Ikeda, Y., Rosenblatt, J., Avigan, D. E., Teruya-Feldstein, J., & Pandolfi, P. P. (2008). PML targeting eradicates quiescent leukaemia-initiating cells. Nature, 453(7198), 1072-1078. https://doi.org/10.1038/nature07016