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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Peggy Kirstetter
  • Mikkel B. Schuster
  • Oksana Bereshchenko
  • Susan Moore
  • Heidi Dvinge
  • Elke Kurz
  • Kim Theilgaard-Monch
  • Robert Månsson
  • Thomas A. Pedersen
  • Thomas Pabst
  • Evelin Schrock
  • Bo T. Porse
  • Sten Eirik W Jacobsen
  • Paul Bertone
  • Daniel G. Tenen
  • Claus Nerlov
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)299-310
JournalCancer Cell
Volume13
Issue number4
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes