1. The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1 -mutated acute myeloid leukemia
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Papaioannou, Dimitrios, Petri, Andreas, Dovey, Oliver M., Terreri, Sara, Wang, Eric, Collins, Frances A., Woodward, Lauren A., Walker, Allison E., Nicolet, Deedra, Pepe, Felice, Kumchala, Prasanthi, Bill, Marius, Walker, Christopher J., Karunasiri, Malith, Mrózek, Krzysztof, Gardner, Miranda L., Camilotto, Virginia, Zitzer, Nina, Cooper, Jonathan L., Cai, Xiongwei, Rong-Mullins, Xiaoqing, Kohlschmidt, Jessica, Archer, Kellie J., Freitas, Michael A., Zheng, Yi, Lee, Robert J., Aifantis, Iannis, Vassiliou, George, Singh, Guramrit, Kauppinen, Sakari, Bloomfield, Clara D., Dorrance, Adrienne M., and Garzon, Ramiro
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631/67 ,45/91 ,article ,38/90 ,45/88 ,45/15 ,humanities ,3. Good health ,692/4017 ,38/91 ,14/1 ,42/89 ,631/337/572 ,38/89 ,631/337/384 ,38/22 ,631/337 ,38/109 - Abstract
Funder: U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics), Long non-coding RNAs (lncRNAs) are important regulatory molecules that are implicated in cellular physiology and pathology. In this work, we dissect the functional role of the HOXB-AS3 lncRNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 is shown to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism, HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.