Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
AuthorsSomervaille, Tim C P
Matheny, Christina J
Spencer, Gary J
Rinn, John L
Witten, Daniela M
Chang, Howard Y
Shurtleff, Sheila A
Downing, James R
Cleary, Michael L
AffiliationCancer Research UK Leukaemia Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
MetadataShow full item record
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.
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 Cell
JournalCell Stem Cell
- Grist for the MLL: how do MLL oncogenic fusion proteins generate leukemia stem cells?
- Authors: Somervaille TC, Cleary ML
- Issue date: 2010 Jun
- Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential.
- Authors: Wong P, Iwasaki M, Somervaille TC, So CW, Cleary ML
- Issue date: 2007 Nov 1
- Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C.
- Authors: Schwieger M, Schüler A, Forster M, Engelmann A, Arnold MA, Delwel R, Valk PJ, Löhler J, Slany RK, Olson EN, Stocking C
- Issue date: 2009 Sep 17
- Essential role of PU.1 in maintenance of mixed lineage leukemia-associated leukemic stem cells.
- Authors: Aikawa Y, Yamagata K, Katsumoto T, Shima Y, Shino M, Stanley ER, Cleary ML, Akashi K, Tenen DG, Kitabayashi I
- Issue date: 2015 Mar
- Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia.
- Authors: Peng L, Tang Y, Zhang Y, Guo S, Peng L, Ye L, Wang Y, Jiang Y
- Issue date: 2018 Oct