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
{"title":"MALNC：影响AML细胞增殖、成熟和药物反应的新突变NPM1/IDH2R140和pml - rara相关lncRNA","authors":"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","doi":"10.1038/s41417-025-00954-0","DOIUrl":null,"url":null,"abstract":"<p><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 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<sup>R140</sup>/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.</p>","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MALNC: a new mutant NPM1/IDH2<sup>R140</sup> and PML-RARA-associated lncRNA with impact on AML cell proliferation, maturation and drug response.\",\"authors\":\"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\",\"doi\":\"10.1038/s41417-025-00954-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><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 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<sup>R140</sup>/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.</p>\",\"PeriodicalId\":9577,\"journal\":{\"name\":\"Cancer gene therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2025-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer gene therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41417-025-00954-0\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer gene therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41417-025-00954-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
MALNC: a new mutant NPM1/IDH2R140 and PML-RARA-associated lncRNA with impact on AML cell proliferation, maturation and drug response.
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.
期刊介绍：
Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair.
Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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