Javascript verkar inte påslaget? - Vissa delar av Lunds universitets webbplats fungerar inte optimalt utan javascript, kontrollera din webbläsares inställningar.
Du är här

Molecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model.

  • Kristian Reckzeh
  • O Bereshchenko
  • A Mead
  • Matilda Rehn
  • Shabnam Kharazi
  • Sten Eirik W Jacobsen
  • Claus Nerlov
  • Jörg Cammenga
Publiceringsår: 2012
Språk: Engelska
Sidor: 1527-1536
Publikation/Tidskrift/Serie: Leukemia
Volym: 26
Nummer: 7
Dokumenttyp: Artikel i tidskrift
Förlag: Nature Publishing Group


Biallelic CEBPA mutations and FLT3 length mutations are frequently identified in human acute myeloid leukemia (AML) with normal cytogenetics. However, the molecular and cellular mechanisms of oncogene cooperation remain unclear due to a lack of disease models. We have generated an AML mouse model using knockin mouse strains to study cooperation of internal tandem duplication (ITD) mutation in the Flt3 gene with commonly observed C/EBPα mutations. This study provides evidence that FLT3 ITD cooperates in leukemogenesis by enhancing the generation of leukemia-initiating granulocyte-monocyte progenitors (GMP) otherwise prevented by a block in differentiation and skewed lineage priming induced by biallelic C/EBPα mutations. These cellular changes are accompanied by an upregulation of hematopoietic stem cell and STAT5 target genes. By gene expression analysis in premalignant populations we further show a role of FLT3 ITD in activating genes involved in survival/transformation and chemoresistance. Both multipotent progenitors (MPP) and GMP cells contain the potential to induce AML similar to corresponding cells in human AML samples showing that this model resembles human disease.Leukemia accepted article preview online, 9 February 2012; doi:10.1038/leu.2012.37.


  • Cancer and Oncology


  • ISSN: 1476-5551

Box 117, 221 00 LUND
Telefon 046-222 00 00 (växel)
Telefax 046-222 47 20
lu [at] lu [dot] se

Fakturaadress: Box 188, 221 00 LUND
Organisationsnummer: 202100-3211
Om webbplatsen