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@ARTICLE{Zhou:182171,
author = {F. Zhou and N. Aroua$^*$ and Y. Liu and C. Rohde and J.
Cheng and A.-K. Wirth and D. Fijalkowska$^*$ and S. Göllner
and M. Lotze and H. Yun and X. Yu and C. Pabst and T. Sauer
and T. Oellerich and H. Serve and C. Rollig and M.
Bornhauser and C. Thiede and C. Baldus and M. Frye$^*$ and
S. Raffel and J. Krijgsveld$^*$ and I. Jeremias$^*$ and R.
Beckmann and A. Trumpp$^*$ and C. Muller-Tidow},
title = {{A} dynamic r{RNA} ribomethylome drives stemness in acute
myeloid leukemia.},
journal = {Cancer discovery},
volume = {13},
number = {2},
issn = {2159-8274},
address = {Philadelphia, Pa.},
reportid = {DKFZ-2022-02474},
pages = {332-347},
year = {2023},
note = {#EA:A010#LA:A010# / 2023 Feb 6;13(2):332-347},
abstract = {The development and regulation of malignant self-renewal
remains an unresolved issue. Here, we provide biochemical,
genetic, and functional evidence that dynamics in ribosomal
RNA (rRNA) 2'-O-methylation regulate leukemia stem cell
(LSC) activity in vivo. A comprehensive analysis of the rRNA
2'-O-methylation landscape of 94 acute myeloid leukemia
(AML) patients revealed dynamic 2'-O-methylation
specifically at exterior sites of ribosomes. rRNA
2'-O-methylation pattern is closely associated with AML
development stage and LSC gene expression signature. Forced
expression of 2'-O-methyltransferase FBL induced an AML stem
cell phenotype and enabled engraftment of non-LSC leukemia
cells in NSG mice. Enhanced 2'-O-methylation redirected the
ribosome translation program towards amino acid transporter
mRNAs enriched in optimal codons and subsequently increased
intracellular amino acid levels. Methylation at the single
site 18S-guanosine 1447 was instrumental for LSC activity.
Collectively, our work demonstrates that dynamic 2'-O-Me at
specific sites on ribosomal RNAs shifts translational
preferences and controls AML-LSC self-renewal.},
cin = {A010 / B230 / A350 / MU01},
ddc = {610},
cid = {I:(DE-He78)A010-20160331 / I:(DE-He78)B230-20160331 /
I:(DE-He78)A350-20160331 / I:(DE-He78)MU01-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36259929},
doi = {10.1158/2159-8290.CD-22-0210},
url = {https://inrepo02.dkfz.de/record/182171},
}