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@ARTICLE{Hartmann:306830,
author = {M. Hartmann$^*$ and M. Schönung$^*$ and J. Rajak and V.
Maurer$^*$ and L. Hai$^*$ and K. Bauer$^*$ and M.
Hakobyan$^*$ and S. Stäble$^*$ and J. Langstein$^*$ and L.
Jardine and R. Roelz and S. Bohler and E. Khabirova and
A.-H. Maag and D. Vonficht$^*$ and D. Lebrecht and K. M.
Bernt and K. Tan and C. Chen and F. Alikarami and J. Meyer
and J. Wang and T. Boch and N. V. Flore$^*$ and P.
Lutsik$^*$ and M. Milsom$^*$ and S. Raffel and C. Buske and
S. Haas and M. Haniffa and J.-P. Mallm$^*$ and S. Behjati
and M. J. Bonder$^*$ and S. Fröhling$^*$ and E. Stieglitz
and C. M. Niemeyer and J. Hey$^*$ and C. Flotho$^*$ and C.
Plass$^*$ and M. Erlacher$^*$ and M. Schlesner$^*$ and D.
Lipka$^*$},
title = {{M}olecular {P}lasticity {R}esults in {O}ncofetal
{R}eprogramming and {T}herapeutic {V}ulnerabilities in
{J}uvenile {M}yelomonocytic {L}eukemia.},
journal = {Blood cancer discovery},
volume = {nn},
issn = {2643-3230},
address = {Philadelphia, PA},
publisher = {American Association for Cancer Research},
reportid = {DKFZ-2025-02807},
pages = {nn},
year = {2025},
note = {DKFZ-ZMBH Alliance/ #EA:B340#LA:B340#LA:B370#LA:W610# /
epub},
abstract = {Persistent fetal gene expression in childhood neoplasms is
usually explained by a maturation block originating in the
prenatal phase. In contrast, reactivation of fetal genes in
adult malignancies is considered a consequence of oncofetal
reprogramming (OFR) and is associated with aggressive
disease. By reconstructing epigenetic ontogeny in juvenile
myelomonocytic leukemia (JMML), we identified a postnatal
maturation state of JMML stem cells with high
transcriptional plasticity indicative of OFR in high-risk
disease. Similarly, post-natal activation of oncogenic
signaling by inducible Ptpn11E76K mutation in mice,
triggered molecular plasticity and reactivation of fetal
gene expression. Integrative multi-omics analysis revealed
aberrant CD52 expression as a feature of high-risk JMML stem
cells. Anti-CD52 treatment depleted JMML stem cells and
blocked disease propagation in xenograft models. Our results
challenge the prevailing maturation-block model of pediatric
leukemogenesis and establish RAS-associated stem-cell
plasticity as a determinant of OFR and potential therapeutic
vulnerabilities in high-risk JMML.},
subtyp = {Review Article},
cin = {B340 / W192 / A010 / A012 / W610 / B260 / HD01 / FR01 /
B370},
ddc = {610},
cid = {I:(DE-He78)B340-20160331 / I:(DE-He78)W192-20160331 /
I:(DE-He78)A010-20160331 / I:(DE-He78)A012-20160331 /
I:(DE-He78)W610-20160331 / I:(DE-He78)B260-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)FR01-20160331 /
I:(DE-He78)B370-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41348944},
doi = {10.1158/2643-3230.BCD-25-0246},
url = {https://inrepo02.dkfz.de/record/306830},
}