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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                    oncogene has been associated with many types of cancer, including pancreatic, lung, and colorectal. For decades, its gene products were thought to be undruggable. However, during the last decade, a large battery of KRAS inhibitors selective against specific mutations (KRAS\n                    <jats:sup>G12C<\/jats:sup>\n                    and KRAS\n                    <jats:sup>G12D<\/jats:sup>\n                    ), panKRAS inhibitors active against all KRAS isoforms, or even panRAS inhibitors, capable of inhibiting the three members of the RAS family, have been developed. In mice, the\n                    <jats:italic toggle=\"yes\">Kras<\/jats:italic>\n                    locus is essential for embryonic development and can sustain adult homeostasis in the absence of\n                    <jats:italic toggle=\"yes\">Hras<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Nras<\/jats:italic>\n                    expression. Thus, we considered of interest to interrogate the role of the\n                    <jats:italic toggle=\"yes\">Kras<\/jats:italic>\n                    locus in an experimental system to generate potentially relevant information regarding the use of panKRAS or panRAS inhibitors in the clinic. Here, we report that systemic ablation of\n                    <jats:italic toggle=\"yes\">Kras<\/jats:italic>\n                    expression in adult mice does not induce significant changes in overall survival, body weight, glucose levels, metabolic profile, or heart function. In contrast, flow cytometry and histopathological analyses of organs such as blood, bone marrow, and spleen showed a significant increase of the myeloid lineage leading to myelomonocytic metaplasia. In this context, replacement of the KRAS isoforms by HRAS is sufficient to maintain adult homeostasis, suggesting that the unique properties of the\n                    <jats:italic toggle=\"yes\">Kras<\/jats:italic>\n                    locus are primarily due to its pattern of expression rather than to the activity of its gene products.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2512404122","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T03:17:46Z","timestamp":1755573466000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Systemic\n                    <i>Kras<\/i>\n                    ablation disrupts myeloid cell homeostasis in adult mice"],"prefix":"10.1073","volume":"122","author":[{"given":"Elena","family":"Zamorano-Dominguez","sequence":"first","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Morales-Cacho","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Barrero","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Jim\u00e9nez-Parrado","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Dhawahir","sequence":"additional","affiliation":[{"name":"Global Pharma Strategy, F. Hoffmann-La Roche Ltd","place":["Basil, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Hern\u00e1ndez-Porras","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Sim\u00f3n-Carrasco","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Targeted Therapies Group, Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Cient\u00edficas-Universidad de Sevilla-Universidad Pablo de Olavide","place":["Seville, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Barrambana","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pian","family":"Sun","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Galv\u00e1n-del-Rey","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Rosas-Perez","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Liaki","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Drosten","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"name":"RAS Signalling and Lung Cancer Group, Molecular Mechanisms of Cancer Program, Centro de Investigaci\u00f3n del C\u00e1ncer, Consejo Superior de Investigaciones Cient\u00edficas-Universidad de Salamanca","place":["Salamanca, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Musteanu","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Universidad Complutense de Madrid","place":["Madrid, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Virga","sequence":"additional","affiliation":[{"name":"Experimental Oncology Group, Molecular Oncology Program, Centro Nacional de Investigaciones Oncol\u00f3gicas","place":["Madrid, Spain"]},{"name":"Inmunobiology Unit, Centro Nacional de Investigaciones Cardiovasculares","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0321","authenticated-orcid":false,"given":"Eugenio","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, 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Canelles, Regulation of c-Myc and Max in megakaryocytic and monocytic-macrophagic differentiation of K562 cells induced by protein kinase C modifiers: c-Myc is down-regulated but does not inhibit differentiation. Cell Growth Differ. 10, 639\u2013654 (1999).","journal-title":"Cell Growth Differ."},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.56.070187.004023"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400397"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1748"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/17446651.2017.1361821"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.995013"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98197"},{"key":"e_1_3_5_33_2","doi-asserted-by":"crossref","unstructured":"B. S. 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