Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/53373
Title:
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Authors:
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
Abstract:
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.
Affiliation:
Cancer Research UK Leukaemia Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Citation:
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. 2009, 4 (2):129-40 Cell Stem Cell
Journal:
Cell Stem Cell
Issue Date:
6-Feb-2009
URI:
http://hdl.handle.net/10541/53373
DOI:
10.1016/j.stem.2008.11.015
PubMed ID:
19200802
Type:
Article
Language:
en
ISSN:
1934-5909
Appears in Collections:
All Paterson Institute for Cancer Research; Leukaemia Biology Group

Full metadata record

DC FieldValue Language
dc.contributor.authorSomervaille, Tim C P-
dc.contributor.authorMatheny, Christina J-
dc.contributor.authorSpencer, Gary J-
dc.contributor.authorIwasaki, Masayuki-
dc.contributor.authorRinn, John L-
dc.contributor.authorWitten, Daniela M-
dc.contributor.authorChang, Howard Y-
dc.contributor.authorShurtleff, Sheila A-
dc.contributor.authorDowning, James R-
dc.contributor.authorCleary, Michael L-
dc.date.accessioned2009-03-09T15:18:58Z-
dc.date.available2009-03-09T15:18:58Z-
dc.date.issued2009-02-06-
dc.identifier.citationHierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. 2009, 4 (2):129-40 Cell Stem Cellen
dc.identifier.issn1934-5909-
dc.identifier.pmid19200802-
dc.identifier.doi10.1016/j.stem.2008.11.015-
dc.identifier.urihttp://hdl.handle.net/10541/53373-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subjectMyeloid Leukaemiaen
dc.subjectStem Cellsen
dc.subjectEmbryonic Stem Cellsen
dc.subjectAdult Stem Cellsen
dc.titleHierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Leukaemia Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.en
dc.identifier.journalCell Stem Cellen

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