{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:46:19Z","timestamp":1759970779931,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Cancer Society Research Professor Award","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"Margaret Harvey Schering Trust","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"American Association of Hematology Scholar Award","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"Clinical and Translational Science Institute at the University of Minnesota KL2 Career Development and K to R01 Awards","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"Masonic Cancer Center at the University of Minnesota Translational Working Group, Genetic Mechanisms of Cancer","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"MPre-R01 Brainstorm Awards","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"The Mugee Research Award for Pediatric Cancer","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"Randy Shaver Cancer Research and Community Fund","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"Division of Hematology, Oncology, and Transplantation, Department of Medicine, the Masonic Cancer Center","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]},{"name":"University of Minnesota Foundation donors","award":["NIH\/NCATS ULI RR033183","KL2 RR0333182"],"award-info":[{"award-number":["NIH\/NCATS ULI RR033183","KL2 RR0333182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: NRAS mutations are found in approximately 10% of patients with acute myeloid leukemia (AML), with nearly half of those occurring at codon 12, but little is known about how differing G12 mutants affect cancer cell activity. Methods: A novel bioinformatic technique, differential expression and pathway ranking (DEAPR), was used to identify the most prominent changes in terms of both individual genes and associated pathways when comparing AML THP-1 cells containing an NRASG12D mutation with B11 cells, which are THP-1-derived cells with the NRASG12D allele removed and a dox-inducible NRASG12V allele introduced. Results: In total, 1456 differentially expressed (DE) protein-coding genes were uniquely associated to the NRASG12D mutation, while 585 DE protein-coding genes were specific to the NRASG12V mutation. The innate immune system pathway was prominent in both mutant-specific lists, even though the genes involved were not in both lists. Furthermore, the two calprotectin genes (S100A8 and S100A9), also associated with innate immunity, were upregulated in the NRASG12D mutant and downregulated in the NRASG12V mutant. Conclusions: This study, using the DEAPR strategy, clearly demonstrates the dramatic changes associated with two seemingly similar NRAS mutations, suggesting the deployment of different treatment strategies based on the type of NRAS mutation present.<\/jats:p>","DOI":"10.3390\/cancers17030467","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T11:08:23Z","timestamp":1738235303000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DEAPR: Differential Expression and Pathway Ranking Tool Demonstrates NRASG12V and NRASG12D Mutations Have Differing Effects in THP-1 Cells"],"prefix":"10.3390","volume":"17","author":[{"given":"Susan K.","family":"Rathe","sequence":"first","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy P.","family":"White","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohar","family":"Sachs","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3183-0491","authenticated-orcid":false,"given":"David A.","family":"Largaespada","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1073\/pnas.80.8.2112","article-title":"Three human transforming genes are related to the viral ras oncogenes","volume":"80","author":"Shimizu","year":"1983","journal-title":"Proc. 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