PML targeting eradicates quiescent leukaemia-initiating cells Journal Article
| Authors: | Ito, K.; Bernardi, R.; Morotti, A.; Matsuoka, S.; Saglio, G.; Ikeda, Y.; Rosenblatt, J.; Avigan, D. E.; Teruya-Feldstein, J.; Pandolfi, P. P. |
| Article Title: | PML targeting eradicates quiescent leukaemia-initiating cells |
| 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. ©2008 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | adult; controlled study; human tissue; protein expression; nonhuman; protein function; animal cell; mouse; cytology; animals; mice; protein targeting; cell line; animal experiment; recurrence; mice, inbred c57bl; transcription factors; nuclear proteins; regeneration; cancer inhibition; arsenicals; oxides; gene expression regulation, neoplastic; neoplastic stem cells; leukemia cell; tumor suppressor proteins; hematopoietic stem cells; hematopoietic stem cell; tumor; leukemia, myelogenous, chronic, bcr-abl positive; disease treatment; coculture techniques; promyelocytic leukemia protein; drug; blood system disorder |
| Journal Title: | Nature |
| Volume: | 453 |
| Issue: | 7198 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-05-19 |
| Start Page: | 1072 |
| End Page: | 1078 |
| Language: | English |
| DOI: | 10.1038/nature07016 |
| PUBMED: | 18469801 |
| PROVIDER: | scopus |
| PMCID: | PMC2712082 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 129" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work