{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:01:09Z","timestamp":1780048869898,"version":"3.53.1"},"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013885","name":"Kementerian Kesihatan Malaysia","doi-asserted-by":"publisher","award":["NMRR 17-1929-36614"],"award-info":[{"award-number":["NMRR 17-1929-36614"]}],"id":[{"id":"10.13039\/501100013885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003782","name":"Institute of Postgraduate Studies, Universiti Sains Malaysia","doi-asserted-by":"publisher","award":["GIPS-PhD 311\/PPSP\/4404814"],"award-info":[{"award-number":["GIPS-PhD 311\/PPSP\/4404814"]}],"id":[{"id":"10.13039\/501100003782","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Acute myeloid leukaemia-normal karyotype (AML-NK) exhibits heterogeneity in expression profiles, influencing the treatment response and survival outcome. Transcriptome sequencing allows a comprehensive analysis of differentially expressed genes (DEGs) and dysregulated pathways in AML-NK, shedding light on the molecular mechanisms and their implications in patients\u2019 management. DEG analyses utilising transcriptome sequencing were conducted using a customised DESeq2 pipeline on 51 AML-NK patients at diagnosis (DX), 12 AML-NK patients who attained first remission (CR1) and 12 healthy controls. The transcriptomic sequencing of AML-NK compared to healthy controls revealed 5,126 DEGs, comprising 85.8% coding genes and 14.2% non-coding elements across 37 pathway categories. The AML-NK DX versus CR1 identified 5,621 DEGs consisting of 84.7% coding genes and 15.3% non-coding elements affecting 20 categories of pathways. Gene set enrichment analysis in this study revealed consistent upregulation of proliferative pathways, including cell cycle and DNA replication. In contrast, immune-related pathways, such as cytokine-cytokine receptor interactions and MHC antigen presentation pathways, were downregulated. Overexpression of oncogenes (<jats:italic>FLT3, MYB, DNMT3B, and MYCN<\/jats:italic>) in DX vs CR1 samples reinforces their usefulness in minimal residual disease monitoring, especially in AML-NK with no genetic aberrations. These findings reiterate the known hallmarks of cancers and validate the transcriptomic dysregulation in the pathogenesis of AML-NK. The robustness of the transcriptome sequencing findings was confirmed by RT-qPCR validation of six genes that were not reported in AML-NK patients. The comprehensive analyses of pathways with dysregulation of a myriad of genes led to an understanding of AML-NK pathogenesis and highlighted the markers for minimal residual disease. In summary, this study performed the first transcriptome-wide analysis of AML-NK in a Malaysian cohort and underscored pathways that are candidates for therapeutic interventions.<\/jats:p>","DOI":"10.1371\/journal.pone.0328911","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:34:28Z","timestamp":1757093668000},"page":"e0328911","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gene expression profiling and pathway analysis in acute myeloid leukaemia-normal karyotype patients"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9294-0320","authenticated-orcid":true,"given":"Angeli","family":"Ambayya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-3975","authenticated-orcid":true,"given":"Rozaimi","family":"Razali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Sulong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Yee","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Selvaratnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameela","family":"Sathar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosline","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"issue":"12","key":"pone.0328911.ref001","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute Myeloid Leukemia","volume":"373","author":"H D\u00f6hner","year":"2015","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0328911.ref002","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s11912-012-0252-x","article-title":"Acute myeloid leukemia with normal cytogenetics","volume":"14","author":"R Mawad","year":"2012","journal-title":"Curr Oncol Rep"},{"issue":"16","key":"pone.0328911.ref003","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJMe048040","article-title":"Gene-expression profiling in acute myeloid leukemia","volume":"350","author":"D Grimwade","year":"2004","journal-title":"N Engl J Med"},{"key":"pone.0328911.ref004","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1182\/asheducation-2009.1.385","article-title":"Independent prognostic factors for AML outcome","author":"D Grimwade","year":"2009","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"4","key":"pone.0328911.ref005","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/bjh.14823","article-title":"Acute myeloid leukaemia genomics","volume":"179","author":"M Medinger","year":"2017","journal-title":"Br J Haematol"},{"issue":"10147","key":"pone.0328911.ref006","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0140-6736(18)31041-9","article-title":"Acute myeloid leukaemia","volume":"392","author":"NJ Short","year":"2018","journal-title":"Lancet"},{"issue":"1","key":"pone.0328911.ref007","first-page":"75","article-title":"Translating cancer genomes and transcriptomes for precision oncology","volume":"66","author":"S Roychowdhury","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"pone.0328911.ref008","unstructured":"Fan Y, Hu Y, Nguyen C, Yan C, Ries RE, Bolouri H. Altered transcriptome uniquely associated with AML vs. normal hematopoiesis. 2017. https:\/\/doi.org\/10.1182\/blood.V130.Suppl_1.3792.3792"},{"issue":"16","key":"pone.0328911.ref009","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJMoa031046","article-title":"Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia","volume":"350","author":"L Bullinger","year":"2004","journal-title":"N Engl J Med"},{"key":"pone.0328911.ref010","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1182\/asheducation-2010.1.47","article-title":"New prognostic markers in acute myeloid leukemia: perspective from the clinic","volume":"2010","author":"JM Foran","year":"2010","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"1","key":"pone.0328911.ref011","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1080\/16078454.2019.1631506","article-title":"Transcriptome analysis identifies key regulators and networks in Acute 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Schurch","year":"2016","journal-title":"RNA"},{"issue":"7","key":"pone.0328911.ref021","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Y Liao","year":"2014","journal-title":"Bioinformatics"},{"issue":"12","key":"pone.0328911.ref022","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"2","key":"pone.0328911.ref023","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/biostatistics\/kxs033","article-title":"A new shrinkage estimator for dispersion improves differential expression detection in RNA-seq data","volume":"14","author":"H Wu","year":"2013","journal-title":"Biostatistics"},{"key":"pone.0328911.ref024","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz401","article-title":"WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs","volume":"47","author":"Y Liao","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"17","key":"pone.0328911.ref025","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"S Chen","year":"2018","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0328911.ref026","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0328911.ref027","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of 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Zhuang","year":"2020","journal-title":"PeerJ"},{"key":"pone.0328911.ref037","doi-asserted-by":"crossref","first-page":"1946703","DOI":"10.1155\/2023\/1946703","article-title":"Exploring Prognostic Biomarkers of Acute Myeloid Leukemia to Determine Its Most Effective Drugs from the FDA-Approved List through Molecular Docking and Dynamic Simulation","volume":"2023","author":"MM Alom","year":"2023","journal-title":"Biomed Res Int"},{"key":"pone.0328911.ref038","doi-asserted-by":"crossref","first-page":"2040620720958586","DOI":"10.1177\/2040620720958586","article-title":"High CXCR2 expression predicts poor prognosis in adult patients with acute myeloid leukemia","volume":"11","author":"W Tang","year":"2020","journal-title":"Ther Adv Hematol"},{"issue":"1","key":"pone.0328911.ref039","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/s42003-022-04139-5","article-title":"The methyltransferase domain of DNMT1 is an essential domain in acute myeloid leukemia independent of DNMT3A mutation","volume":"5","author":"B Bhogal","year":"2022","journal-title":"Commun Biol"},{"issue":"1","key":"pone.0328911.ref040","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12967-021-02733-5","article-title":"The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia","volume":"19","author":"C Han","year":"2021","journal-title":"J Transl Med"},{"key":"pone.0328911.ref041","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/01.HS9.0000562220.27971.d0","article-title":"PS980 GRIK5 drives self renewal pathways in human acute myeloid LEUKEMIA CELLS","volume":"3","author":"J Xia","year":"2019","journal-title":"HemaSphere"},{"key":"pone.0328911.ref042","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1182\/blood-2019-131518","article-title":"Mir-29 Maintains the Acute Myeloid Leukemia Epigenome By Regulating CBX2","volume":"134","author":"CJ 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Sariani","year":"2021","journal-title":"Cytokine"},{"issue":"4","key":"pone.0328911.ref062","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.soc.2007.08.004","article-title":"Tumor microenvironment and immune escape","volume":"16","author":"S Ferrone","year":"2007","journal-title":"Surg Oncol Clin N Am"},{"key":"pone.0328911.ref063","doi-asserted-by":"crossref","first-page":"717616","DOI":"10.3389\/fonc.2021.717616","article-title":"Integrative Analysis of Gene Expression Data by RNA Sequencing for Differential Diagnosis of Acute Leukemia: Potential Application of Machine Learning","volume":"11","author":"J Lee","year":"2021","journal-title":"Front Oncol"},{"issue":"8","key":"pone.0328911.ref064","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.21037\/tcr-23-85","article-title":"Exploring prognostic markers for patients with acute myeloid leukemia based on cuproptosis related genes","volume":"12","author":"X Li","year":"2023","journal-title":"Transl Cancer Res"},{"issue":"2","key":"pone.0328911.ref065","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1189\/jlb.0209097","article-title":"MAPK signaling pathways in the regulation of hematopoiesis","volume":"86","author":"CR Geest","year":"2009","journal-title":"J Leukoc Biol"},{"issue":"3","key":"pone.0328911.ref066","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.3390\/ijms21031102","article-title":"Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity","volume":"21","author":"S Lee","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"7","key":"pone.0328911.ref067","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.3390\/cancers12071760","article-title":"MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy","volume":"12","author":"AM Cornel","year":"2020","journal-title":"Cancers 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