PML targeting eradicates quiescent leukaemia-initiating cells
Copyright policy )PML targeting eradicates quiescent leukaemia-initiating cells
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.
- University of Turin Italy
- Harvard University United States
- Beth Israel Deaconess Medical Center United States
- Keio University Japan
- Memorial Sloan Kettering Cancer Center United States
Adult, Male, Nuclear Proteins, Oxides, Promyelocytic Leukemia Protein, Hematopoietic Stem Cells, Arsenicals, Coculture Techniques, Cell Line, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Mice, Arsenic Trioxide, Recurrence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplastic Stem Cells, Animals, Humans, Regeneration, Female
Adult, Male, Nuclear Proteins, Oxides, Promyelocytic Leukemia Protein, Hematopoietic Stem Cells, Arsenicals, Coculture Techniques, Cell Line, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Mice, Arsenic Trioxide, Recurrence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplastic Stem Cells, Animals, Humans, Regeneration, Female
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