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<p>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 <i>myeloid and AML-associated intergenic long non-coding RNA</i> (MALNC). MALNC is overexpressed in AML, particularly in cases with the <i>PML-RARA</i> fusion or <i>IDH2</i><sup><i>R140</i></sup><i>/NPM1</i> co-mutations, and is associated with a distinct gene expression profile. Functional studies showed that <i>MALNC</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月23日

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  • Elisabetta Cozzi,
  • Anne Neddermeyer,
  • Xiangfu Zhong,
  • Angelica 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,
  • Jiri Bartek,
  • Olli-Pekka Kallioniemi,
  • Hong Qian,
  • Andreas Lennartsson,
  • Sören Lehmann

摘要

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 IDH2R140/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.