%0 Journal Article
%A Zhou, Fengbiao
%A Aroua, Nesrine
%A Liu, Yi
%A Rohde, Christian
%A Cheng, Jingdong
%A Wirth, Anna-Katharina
%A Fijalkowska, Daria
%A Göllner, Stefanie
%A Lotze, Michelle
%A Yun, Haiyang
%A Yu, Xiaobing
%A Pabst, Caroline
%A Sauer, Tim
%A Oellerich, Thomas
%A Serve, Hubert
%A Rollig, Christoph
%A Bornhauser, Martin
%A Thiede, Christian
%A Baldus, Claudia
%A Frye, Michaela
%A Raffel, Simon
%A Krijgsveld, Jeroen
%A Jeremias, Irmela
%A Beckmann, Roland
%A Trumpp, Andreas
%A Muller-Tidow, Carsten
%T A dynamic rRNA ribomethylome drives stemness in acute myeloid leukemia.
%J Cancer discovery
%V 13
%N 2
%@ 2159-8274
%C Philadelphia, Pa.
%M DKFZ-2022-02474
%P 332-347
%D 2023
%Z #EA:A010#LA:A010# / 2023 Feb 6;13(2):332-347
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36259929
%R 10.1158/2159-8290.CD-22-0210
%U https://inrepo02.dkfz.de/record/182171