000K utf8 1100 2021$c2021-08-31 1500 eng 2050 urn:nbn:de:gbv:27-dbt-20230327-203343-005 2051 10.1038/s41375-021-01393-0 3000 Perner, Florian 3010 Armstrong, Scott A. 3010 Brandt, Sabine 3010 Eifert, Theresa 3010 Hartmann, Maximilian 3010 Hatton, Charles 3010 Heidel, Florian H. 3010 Hochhaus, Andreas 3010 Hoell, Jessica I. 3010 Huber, Nicolas 3010 Jayavelu, Ashok Kumar 3010 Mandinova, Anna 3010 Mann, Matthias 3010 Mashamba, Nomusa 3010 Mertens, Peter R. 3010 Murphy, Ciara 3010 Perner, Birgit 3010 Santamaria, Nuria Tubio 3010 Schnoeder, Tina M. 3010 Schröder, Nicolas 3010 Todorova, Kristina 3010 Xiong, Yijun 4000 YBX1 mediates translation of oncogenic transcripts to control cell competition in AML [Perner, Florian] 4060 12 Seiten 4209 Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2 -mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression. 4950 https://doi.org/10.1038/s41375-021-01393-0$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:27-dbt-20230327-203343-005$xR$3Volltext$534 4961 https://www.db-thueringen.de/receive/dbt_mods_00056518 5051 610 5550 Acute myeloid leukaemia 5550 Cancer stem cells