The functional role of snoRNAs in NPM1 wildtype and mutant AML

• Applicant: Fengbiao Zhou, Ph.D.
• Subject Area: Hematology, Oncology ; Biochemistry ; Cell Biology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413674146

• Final Report Year: 2022

Final Report Abstract

In this project, we established the first ribomethylome landscape in human AML and normal hematopoietic cells. We identified a critical role for dynamic snoRNA directed rRNA 2’-O-Me in governing protein translation and cancer stem cell phenotypes. This study not only expands our knowledge about AML pathology, but also sheds light on a new regulatory mechanism of gene expression conferred by rRNA modifications. Lastly and most importantly, we found that SNORD127 could be a new potential therapeutic target in AML. Based on these data, we are developing therapeutic approaches targeting SNORD127 in AML.

Publications

• Site-specific methylation of 18S ribosomal RNA by SNORD42A is required for acute myeloid leukemia cell proliferation. Blood, 135(23), 2059-2070.
  Pauli, Cornelius; Liu, Yi; Rohde, Christian; Cui, Chunhong; Fijalkowska, Daria; Gerloff, Dennis; Walter, Carolin; Krijgsveld, Jeroen; Dugas, Martin; Edemir, Bayram; Pabst, Caroline; Müller, Lutz P.; Zhou, Fengbiao & Müller-Tidow, Carsten
  
• A Dynamic rRNA Ribomethylome Drives Stemness in Acute Myeloid Leukemia. Cancer Discovery, 13(2), 332-347.
  Zhou, Fengbiao; Aroua, Nesrine; Liu, Yi; Rohde, Christian; Cheng, Jingdong; Wirth, Anna-Katharina; Fijalkowska, Daria; Göllner, Stefanie; Lotze, Michelle; Yun, Haiyang; Yu, Xiaobing; Pabst, Caroline; Sauer, Tim; Oellerich, Thomas; Serve, Hubert; Röllig, Christoph; Bornhäuser, Martin; Thiede, Christian; Baldus, Claudia ... & Müller-Tidow, Carsten