1. Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology,
2. Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
3. Cancer Biology and Genetics Program,
4. Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
5. Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan
6. Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin 10043, Italy

Correspondence to: Pier Paolo Pandolfi^1,3,4 Correspondence and requests for materials should be addressed to P.P.P. (Email: ppandolf@bidmc.harvard.edu).

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.

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