The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis.
The homeobox transcription factor CDX2 plays an important role in embryonic development and regulates the proliferation and differentiation of intestinal epithelial cells in the adult. We have found that CDX2 is expressed in leukemic cells of 90% of patients with acute myeloid leukemia (AML) but not in hematopoietic stem and progenitor cells derived from normal individuals. Stable knockdown of CDX2 expression by RNA interference inhibited the proliferation of various human AML cell lines and strongly reduced their clonogenic potential in vitro. Primary murine hematopoietic progenitor cells transduced with Cdx2 acquired serial replating activity, were able to be continuously propagated in liquid culture, generated fully penetrant and transplantable AML in BM transplant recipients, and displayed dysregulated expression of Hox family members in vitro and in vivo. These results demonstrate that aberrant expression of the developmental regulatory gene CDX2 in the adult hematopoietic compartment is a frequent event in the pathogenesis of AML; suggest a role for CDX2 as part of a common effector pathway that promotes the proliferative capacity and self-renewal potential of myeloid progenitor cells; and support the hypothesis that CDX2 is responsible, in part, for the altered HOX gene expression that is observed in most cases of AML.
Scholl
Claudia
C
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bansal
Dimple
D
Döhner
Konstanze
K
Eiwen
Karina
K
Huntly
Brian J P
BJ
Lee
Benjamin H
BH
Rücker
Frank G
FG
Schlenk
Richard F
RF
Bullinger
Lars
L
Döhner
Hartmut
H
Gilliland
D Gary
DG
Fröhling
Stefan
S
D016026:Bone Marrow Transplantation / Q000473:pathology / Q000502:physiology; D000071616:CDX2 Transcription Factor; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D034622:RNA Interference; D014178:Translocation, Genetic
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins