{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:42:01Z","timestamp":1762065721902,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Free University of Bozen-Bolzano, Italy","award":["DAQETA-CML","4-157-3-052"],"award-info":[{"award-number":["DAQETA-CML","4-157-3-052"]}]},{"name":"Qatar National Research Fund","award":["DAQETA-CML","4-157-3-052"],"award-info":[{"award-number":["DAQETA-CML","4-157-3-052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context.<\/jats:p>","DOI":"10.3390\/ijms23179899","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T01:50:51Z","timestamp":1661997051000},"page":"9899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gene Expression Landscape of Chronic Myeloid Leukemia K562 Cells Overexpressing the Tumor Suppressor Gene PTPRG"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6953-5447","authenticated-orcid":false,"given":"Giulia","family":"Lombardi","sequence":"first","affiliation":[{"name":"Faculty of Computer Science, Free University of Bozen-Bolzano, Piazza Domenicani 3, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6722-5683","authenticated-orcid":false,"given":"Roberta Valeria","family":"Latorre","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2323-3344","authenticated-orcid":false,"given":"Alessandro","family":"Mosca","sequence":"additional","affiliation":[{"name":"Faculty of Computer Science, Free University of Bozen-Bolzano, Piazza Domenicani 3, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Calvanese","sequence":"additional","affiliation":[{"name":"Faculty of Computer Science, Free University of Bozen-Bolzano, Piazza Domenicani 3, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Tomasello","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy"},{"name":"Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-4100","authenticated-orcid":false,"given":"Christian","family":"Boni","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-6887","authenticated-orcid":false,"given":"Manuela","family":"Ferracin","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Negrini","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Traslazionale e per la Romagna, University of Ferrara Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-1135","authenticated-orcid":false,"given":"Nader Al","family":"Dewik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neonatology, Neonatal Intensive Care Unit, Newborn Screening Unit, Women\u2019s Wellness and Research Center, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Genomics and Precision Medicine (GPM), College of Health & Life Science (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"},{"name":"Department of Research, Women\u2019s Wellness and Research Center, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Interim Translational Research Institute (iTRI), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"School of Life Science, Pharmacy and Chemistry, Faculty of Science, Engineering & Computing, Kingston University, Kingston University London, River House, 53\u201357 High Street, Kingston upon Thames, London KT1 1LQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-8076","authenticated-orcid":false,"given":"Mohamed","family":"Yassin","sequence":"additional","affiliation":[{"name":"School of Life Science, Pharmacy and Chemistry, Faculty of Science, Engineering & Computing, Kingston University, Kingston University London, River House, 53\u201357 High Street, Kingston upon Thames, London KT1 1LQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7647-856X","authenticated-orcid":false,"given":"Mohamed A.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Interim Translational Research Institute (iTRI), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"School of Life Science, Pharmacy and Chemistry, Faculty of Science, Engineering & Computing, Kingston University, Kingston University London, River House, 53\u201357 High Street, Kingston upon Thames, London KT1 1LQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-0033","authenticated-orcid":false,"given":"Bruno","family":"Carpentieri","sequence":"additional","affiliation":[{"name":"Faculty of Computer Science, Free University of Bozen-Bolzano, Piazza Domenicani 3, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-4014","authenticated-orcid":false,"given":"Claudio","family":"Sorio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of General Pathology, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Lecca","sequence":"additional","affiliation":[{"name":"Faculty of Computer Science, Free University of Bozen-Bolzano, Piazza Domenicani 3, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1016\/S0140-6736(21)01204-6","article-title":"Chronic myeloid leukaemia","volume":"398","author":"Cortes","year":"2021","journal-title":"The Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00277-015-2327-x","article-title":"Response-related predictors of survival in CML","volume":"94","author":"Hanfstein","year":"2015","journal-title":"Ann. 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