AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia.

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autor(en): Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Koehn M, Misiak D, Baeumer N, Cui C, Goellner S, Oellerich T, Serve H, Garcia-Cuellar MP, Slany R, Maciejewski JP, Przychodzen B, Seliger B, Klein HU, Bartenhagen C, Berdel WE, Dugas M, Taketo MM, Farouq D, Schwartz S, Regev A, Hebert J, Sauvageau G, Pabst C, Huettelmaier S, Mueller-Tidow C
Zeitschrift: Nature Cell Biology
Jahr der Veröffentlichung: 2017
Band: 19
Heftnummer: 7
Seitenbereich: 844-855
ISSN: 1476-4679


Abstract


Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential. Genomic deletion of either C/D box snoRNA SNORD14D or SNORD35A suppressed clonogenic potential of leukaemia cells in vitro and delayed leukaemogenesis in vivo. We further showed that AML1-ETO9a, MYC and MLL-AF9 all enhanced snoRNA formation. Expression levels of C/D box snoRNAs in AML patients correlated closely with in vivo frequency of leukaemic stem cells. Collectively, these findings indicate that induction of C/D box snoRNA/RNP function constitutes an important pathway in leukaemogenesis.



FAU-Autoren / FAU-Herausgeber

Garcia-Cuellar, Maria-Paz Dr.
Lehrstuhl für Genetik
Slany, Robert Prof. Dr.
Lehrstuhl für Genetik


Autor(en) der externen Einrichtung(en)
Cleveland Clinic
Eli and Edythe L. Broad Institute of MIT and Harvard
Goethe-Universität Frankfurt am Main
Hôpital Maisonneuve-Rosemont
Kyoto University / 京都大学 Kyōto daigaku
Martin-Luther-Universität Halle-Wittenberg (MLU)
Westfälische Wilhelms-Universität (WWU) Münster


Zitierweisen

APA:
Zhou, F., Liu, Y., Rohde, C., Pauli, C., Gerloff, D., Koehn, M.,... Mueller-Tidow, C. (2017). AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Nature Cell Biology, 19(7), 844-855. https://dx.doi.org/10.1038/ncb3563

MLA:
Zhou, Fengbiao, et al. "AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia." Nature Cell Biology 19.7 (2017): 844-855.

BibTeX: 

Zuletzt aktualisiert 2018-06-11 um 20:50