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Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Runx1/AML1 is a Guardian of Hematopoietic Stem Cells

Author(s): Lena Motoda, Motomi Osato and Yoshiaki Ito

Volume 4, Issue 3, 2008

Page: [188 - 195] Pages: 8

DOI: 10.2174/157339408785294302

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


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