IWASAKI Masayuki
Department Research Institutes and Facilities, Research Institutes and Facilities Position Assistant Professor |
|
Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. |
Journal | Formal name:Cell stem cell Abbreviation:Cell Stem Cell ISSN code:18759777/18759777 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 4(2),pp.129-40 |
Author and coauthor | Somervaille Tim C P, Matheny Christina J, Spencer Gary J, Iwasaki Masayuki, Rinn John L, Witten Daniela M, Chang Howard Y, Shurtleff Sheila A, Downing James R, Cleary Michael L |
Publication date | 2009/02 |
Summary | The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional subprogram more akin to that of embryonic stem cells (ESCs) than to that of adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3, and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when coexpressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia-initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor-prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells (CSCs) to prognosis in human cancer. |
DOI | 10.1016/j.stem.2008.11.015 |
PMID | 19200802 |