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

Summary, in English

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.

• Författare: 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
• Avdelning/ar: Stamcellscentrum (SCC)
• Publiceringsår: 2008
• Språk: Engelska
• Sidor: 299-310
• Publikation/Tidskrift/Serie: Cancer Cell
• Volym: 13
• Issue: 4
• Länkar: http://dx.doi.org/10.1016/j.ccr.2008.02.008
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Cancer and Oncology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1878-3686