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Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia

Zhang, Hong; Alberich-Jorda, Meritxell; Amabile, Giovanni; Yang, Henry; Staber, Philipp B.; DiRuscio, Annalisa; Welner, Robert S.; Ebralidze, Alexander; Zhang, Junyan and Levantini, Elena, et al. (2013) In Cancer Cell 24(5). p.575-588
Abstract
Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4... (More)
Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype. (Less)
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published
subject
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Cancer Cell
volume
24
issue
5
pages
575 - 588
publisher
Cell Press
external identifiers
  • wos:000327005100006
  • scopus:84887553701
ISSN
1878-3686
DOI
10.1016/j.ccr.2013.09.018
language
English
LU publication?
yes
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de0fc227-a8ff-4722-947a-0b9e9da0a9d5 (old id 4196728)
date added to LUP
2014-01-02 11:55:31
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2019-05-21 01:10:54
@article{de0fc227-a8ff-4722-947a-0b9e9da0a9d5,
  abstract     = {Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBP alpha whereby its expression is inversely correlated with C/EBP alpha activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype.},
  author       = {Zhang, Hong and Alberich-Jorda, Meritxell and Amabile, Giovanni and Yang, Henry and Staber, Philipp B. and DiRuscio, Annalisa and Welner, Robert S. and Ebralidze, Alexander and Zhang, Junyan and Levantini, Elena and Lefebvre, Veronique and Valk, Peter J. M. and Delwel, Ruud and Hoogenkamp, Maarten and Nerlov, Claus and Cammenga, Jörg and Saez, Borja and Scadden, David T. and Bonifer, Constanze and Ye, Min and Tenen, Daniel G.},
  issn         = {1878-3686},
  language     = {eng},
  number       = {5},
  pages        = {575--588},
  publisher    = {Cell Press},
  series       = {Cancer Cell},
  title        = {Sox4 Is a Key Oncogenic Target in C/EBP alpha Mutant Acute Myeloid Leukemia},
  url          = {http://dx.doi.org/10.1016/j.ccr.2013.09.018},
  volume       = {24},
  year         = {2013},
}