Abstract 519: The long non-coding RNA (lncRNA) HOXB-AS3 regulates transcription of ribosomal RNA (rRNA) in NPM1-mutated (NPM1mut) acute myeloid leukemia (AML)

Background: A HOXB-locus-embedded lncRNA, named HOXB-AS3 significantly associates with NPM1 mutations in AML. Herein, we evaluate the functional role of HOXB-AS3 expression in NPM1mut AML. Methods: HOXB-AS3 expression was measured by real-time PCR. Knock-down (KD) of HOXB-AS3 was performed in vitro and in vivo with locked nucleic acid-modified gapmers. RNA antisense purification (RAP), RNA-immunoprecipitation (RIP), and Chromatin-immunoprecipitation (ChIP) experiments were performed according to published protocols. Results: Among 7 AML cell lines tested, only OCI-AML3 cells, which harbor NPM1mut, showed detectable HOXB-AS3 expression. HOXB-AS3 was more abundant in NPM1mut AML patient (pt) blasts than blasts of AML pts with wild-type NPM1 (P=.001) and bone marrow samples from healthy donors(P=.001). HOXB-AS3 localized in the nucleus and did not associate with isolated polysomes of OCI-AML3 cells. In vitro HOXB-AS3 KD in OCI-AML3 cells decreased the cells in S phase (P Conclusions: We describe the function of the HOXB-AS3 lncRNA as a compensatory mechanism, which mediates increased rRNA transcription and adequate protein production, in NPM1mut AML. From a therapeutic standpoint, we show that HOXB-AS3-targeting yields anti-leukemic activity in pre-clinical models. Citation Format: Dimitrios Papaioannou, Andreas Petri, Sara Terreri, Charlotte A. Thrue, Deedra Nicolet, Frances A. Collins, Lauren A. Woodward, Prasanthi Kumchala, Malith Karunasiri, Felice Pepe, Marius Bill, Nina Zitzer, Guramrit Singh, Sakari Kaupinnen, Clara D. Bloomfield, Adrienne M. Dorrance, Ramiro Garzon. The long non-coding RNA (lncRNA) HOXB-AS3 regulates transcription of ribosomal RNA (rRNA) in NPM1 -mutated ( NPM1 mut) acute myeloid leukemia (AML) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 519.