Abstract
An oncogenic stimulus in a cell primarily results in hyperproliferation. However, uncontrolled cell proliferation is sensed by the cell and triggers a fail-safe mechanism resulting in senescence, apoptosis, or differentiation. This phenomenon is considered to be a cellular fail-safe mechanism to eliminate undesirable cells from a population of healthy cells. The RUNX1/AML1 gene, one of the most frequently targeted genes in human leukemia, is induced by the Ras oncogene in hematopoietic stem/progenitor cells and required to maintain the fail-safe mechanism. The stem cell pool is thereby protected from oncogenic insults and cancer-initiating cells, which would become cancer stem cells after accumulation of sequential genetic changes, are eliminated. This fail-safe mechanism and the consequence of its disruption in oncogenesis seems to be a fundamentally important concept, but have not been fully recognized to date. Gaining a better understanding of this mechanism might lead to new strategies to treat cancer stem cell-associated resistance to chemotherapy which is the subject of intense discussion in recent years.
Keywords: Runx, leukemia stem cell, cancer stem cell, senescence, apoptosis
Current Cancer Therapy Reviews
Title: Runx1/AML1 is a Guardian of Hematopoietic Stem Cells
Volume: 4 Issue: 3
Author(s): Lena Motoda, Motomi Osato and Yoshiaki Ito
Affiliation:
Keywords: Runx, leukemia stem cell, cancer stem cell, senescence, apoptosis
Abstract: An oncogenic stimulus in a cell primarily results in hyperproliferation. However, uncontrolled cell proliferation is sensed by the cell and triggers a fail-safe mechanism resulting in senescence, apoptosis, or differentiation. This phenomenon is considered to be a cellular fail-safe mechanism to eliminate undesirable cells from a population of healthy cells. The RUNX1/AML1 gene, one of the most frequently targeted genes in human leukemia, is induced by the Ras oncogene in hematopoietic stem/progenitor cells and required to maintain the fail-safe mechanism. The stem cell pool is thereby protected from oncogenic insults and cancer-initiating cells, which would become cancer stem cells after accumulation of sequential genetic changes, are eliminated. This fail-safe mechanism and the consequence of its disruption in oncogenesis seems to be a fundamentally important concept, but have not been fully recognized to date. Gaining a better understanding of this mechanism might lead to new strategies to treat cancer stem cell-associated resistance to chemotherapy which is the subject of intense discussion in recent years.
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Cite this article as:
Motoda Lena, Osato Motomi and Ito Yoshiaki, Runx1/AML1 is a Guardian of Hematopoietic Stem Cells, Current Cancer Therapy Reviews 2008; 4 (3) . https://dx.doi.org/10.2174/157339408785294302
DOI https://dx.doi.org/10.2174/157339408785294302 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
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