Abstract
Id1 is frequently overexpressed in many cancer cells, but the functional significance of these findings is not known. To determine if Id1 could contribute to the development of hematopoietic malignancy, we reconstituted mice with hematopoietic cells overexpressing Id1. We showed for the first time that deregulated expression of Id1 leads to a myeloproliferative disease in mice, and immortalizes myeloid progenitors in vitro. In human cells, we demonstrate that Id genes are expressed in human acute myelogenous leukemia cells, and that knock down of Id1 expression inhibits leukemic cell line growth, suggesting that Id1 is required for leukemic cell proliferation. These findings established a causal relationship between Id1 overexpression and hematologic malignancy. Thus, deregulated expression of Id1 may contribute to the initiation of myeloid malignancy, and Id1 may represent a potential therapeutic target for early stage intervention in the treatment of hematopoietic malignancy.
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Acknowledgements
We gratefully acknowledge the technical support of Steve Stull, Kathleen Noer, Roberta Matthai and Samantha Bauchiero. We also thank Dr Nancy Colburn, Dr Sandra Ruscetti and Dr Kristbjorn Gudmundsson for their critical review of this article. This project has been funded, in part, with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. This research was supported, in part, by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. Clinical specimens were provided by the Sidney Kimmel Cancer Center at Johns Hopkins Tumor and Cell Procurement Bank, supported by the Regional Oncology Research Center Grant no. 5 P30 CA06973.
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Suh, H., Leeanansaksiri, W., Ji, M. et al. Id1 immortalizes hematopoietic progenitors in vitro and promotes a myeloproliferative disease in vivo. Oncogene 27, 5612–5623 (2008). https://doi.org/10.1038/onc.2008.175
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DOI: https://doi.org/10.1038/onc.2008.175
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