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Modeling of C/EBP alpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

Kirstetter, Peggy ; Schuster, Mikkel B. ; Bereshchenko, Oksana ; Moore, Susan ; Dvinge, Heidi ; Kurz, Elke ; Theilgaard-Monch, Kim ; Månsson, Robert LU ; Pedersen, Thomas A. and Pabst, Thomas , et al. (2008) In Cancer Cell 13(4). p.299-310
Abstract
Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBP alpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1(+)c-Kit(+) population that gave rise only to myeloid cells in recipient mice. Expression... (More)
Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBP alpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1(+)c-Kit(+) population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1(+)c-Kit(+) progenitors revealed a signature shared with MLL-AF9-transformed AML. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
13
issue
4
pages
299 - 310
publisher
Cell Press
external identifiers
  • wos:000254817400005
  • scopus:41249103144
  • pmid:18394553
ISSN
1878-3686
DOI
10.1016/j.ccr.2008.02.008
language
English
LU publication?
yes
id
15af4b25-43a1-4126-9ec1-c6b496ce5155 (old id 1207328)
date added to LUP
2016-04-01 12:09:32
date last changed
2022-07-29 23:04:20
@article{15af4b25-43a1-4126-9ec1-c6b496ce5155,
  abstract     = {{Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBP alpha isoform (p42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete penetrance. p42-deficient leukemia could be transferred by a Mac1(+)c-Kit(+) population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1(+)c-Kit(+) progenitors revealed a signature shared with MLL-AF9-transformed AML.}},
  author       = {{Kirstetter, Peggy and Schuster, Mikkel B. and Bereshchenko, Oksana and Moore, Susan and Dvinge, Heidi and Kurz, Elke and Theilgaard-Monch, Kim and Månsson, Robert and Pedersen, Thomas A. and Pabst, Thomas and Schrock, Evelin and Porse, Bo T. and Jacobsen, Sten Eirik W and Bertone, Paul and Tenen, Daniel G. and Nerlov, Claus}},
  issn         = {{1878-3686}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{299--310}},
  publisher    = {{Cell Press}},
  series       = {{Cancer Cell}},
  title        = {{Modeling of C/EBP alpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells}},
  url          = {{http://dx.doi.org/10.1016/j.ccr.2008.02.008}},
  doi          = {{10.1016/j.ccr.2008.02.008}},
  volume       = {{13}},
  year         = {{2008}},
}