MALNC: a new mutant NPM1/IDH2R140 and PML-RARA-associated lncRNA with impact on AML cell proliferation, maturation and drug response

作者：Elisabetta Cozzi, Anne Neddermeyer, Xiangfu Zhong, Angélica María Gamboa-Cedeño, Dimitris C. Kanellis, Albin Österroos, My Björklund, Nona Struyf, Kasper Karlsson, Ying Qu, Alma Månsson, Tatjana Pandzic, Sofia Bengtzén, Christer Nilsson, Roland Fiskesund, Panagiotis Baliakas, Tom Erkers, Jiří Bártek, Olli Kallioniemi, Hong Qian, Andreas Lennartsson, Sören Lehmann · 发表于：Cancer Gene Therapy · 年份：2025 · DOI：10.1038/s41417-025-00954-0 · 被引用次数：2 · 研究领域：Acute Myeloid Leukemia Research、Cancer-related molecular mechanisms research、Immune Cell Function and Interaction

Abstract As the non-coding genome remains poorly characterized in acute myeloid leukemia (AML), we aimed to identify and functionally characterize novel long non-coding RNAs (lncRNAs) relevant to AML biology and treatment. We first identified lncRNAs overexpressed in AML blasts and, among them, discovered a novel transcript, which we named myeloid and AML-associated intergenic long non-coding RNA (MALNC). MALNC is overexpressed in AML, particularly in cases with the PML-RARA fusion or IDH2 R140 /NPM1 co-mutations, and is associated with a distinct gene expression profile. Functional studies showed that MALNC knockout impairs AML cell proliferation and colony formation, enhances ATRA-induced differentiation, and sensitizes cells to arsenic trioxide. Transcriptomic analysis revealed that MALNC loss alters the expression of retinoic acid pathway genes, and chromatin binding studies showed that MALNC binds to genes related to the retinoic acid and Rho GTPase pathways. In conclusion, we have identified MALNC as a novel lncRNA that promotes leukemic cell proliferation, counteracts ATRA-induced differentiation, and modulates drug sensitivity in AML.