Stem cell exhaustion and leukemogenesis |
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Authors: | Bindya Jacob Motomi Osato |
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Institution: | 1. Institute of Molecular and Cell Biology, Singapore 138673, Singapore;2. Cancer Science Institute of Singapore, National University of Singapore, Singapore 117456, Singapore |
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Abstract: | Cancer is the result of a combination of genetic alterations, which aid transformation of cells. However, oncogenic alterations also simultaneously induce some detrimental effects on the cells such as apoptosis, senescence, and differentiation. Such negative effects caused by certain oncogenic events are overcome by other cooperating genetic hits. We propose stem cell exhaustion as a novel detrimental effect that is caused by a wide variety of oncogenic alterations. Interestingly, in most cases, the stem cell exhaustion due to oncogenic alterations is preceded by an abnormal expansion of stem/progenitor cells. This preceding stem/progenitor cell expansion may be a key feature that still promotes cancer development, along with cooperating hits that rescue stem cell exhaustion. This review summarizes current knowledge about hematopoietic stem cell exhaustion and the mechanisms to overcome stem cell exhaustion in cancer development. J. Cell. Biochem. 107: 393–399, 2009. © 2009 Wiley‐Liss, Inc. |
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Keywords: | Runx1 AML1 hematopoietic stem cell niche |
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