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@ARTICLE{Vu:156883,
author = {T. Vu and J. Straube and A. H. Porter and M. Bywater and A.
Song and V. Ling and L. Cooper and G. Pali and C. Bruedigam
and S. Jacquelin and J. Green and G. Magor and A. Perkins
and A. M. Chalk and C. R. Walkley and F. H. Heidel and P.
Mukhopadhyay and N. Cloonan and S. Gröschel$^*$ and J.-P.
Mallm$^*$ and S. Fröhling$^*$ and C. Scholl$^*$ and S. W.
Lane},
title = {{H}ematopoietic stem and progenitor cell-restricted {C}dx2
expression induces transformation to myelodysplasia and
acute leukemia.},
journal = {Nature Communications},
volume = {11},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2020-01190},
pages = {3021},
year = {2020},
abstract = {The caudal-related homeobox transcription factor CDX2 is
expressed in leukemic cells but not during normal blood
formation. Retroviral overexpression of Cdx2 induces AML in
mice, however the developmental stage at which CDX2 exerts
its effect is unknown. We developed a conditionally
inducible Cdx2 mouse model to determine the effects of in
vivo, inducible Cdx2 expression in hematopoietic stem and
progenitor cells (HSPCs). Cdx2-transgenic mice develop
myelodysplastic syndrome with progression to acute leukemia
associated with acquisition of additional driver mutations.
Cdx2-expressing HSPCs demonstrate enrichment of
hematopoietic-specific enhancers associated with
pro-differentiation transcription factors. Furthermore,
treatment of Cdx2 AML with azacitidine decreases leukemic
burden. Extended scheduling of low-dose azacitidine shows
greater efficacy in comparison to intermittent higher-dose
azacitidine, linked to more specific epigenetic modulation.
Conditional Cdx2 expression in HSPCs is an inducible model
of de novo leukemic transformation and can be used to
optimize treatment in high-risk AML.},
cin = {A380 / B066 / W192 / B340 / B290},
ddc = {500},
cid = {I:(DE-He78)A380-20160331 / I:(DE-He78)B066-20160331 /
I:(DE-He78)W192-20160331 / I:(DE-He78)B340-20160331 /
I:(DE-He78)B290-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32541670},
pmc = {pmc:PMC7296000},
doi = {10.1038/s41467-020-16840-2},
url = {https://inrepo02.dkfz.de/record/156883},
}