Rathe Susan K, White Jeremy P, Sachs Zohar, Largaespada David A
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Cancers (Basel). 2025 Jan 30;17(3):467. doi: 10.3390/cancers17030467.
: 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. : 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 mutation with B11 cells, which are THP-1-derived cells with the allele removed and a dox-inducible allele introduced. : In total, 1456 differentially expressed (DE) protein-coding genes were uniquely associated to the mutation, while 585 DE protein-coding genes were specific to the 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 ( and ), also associated with innate immunity, were upregulated in the mutant and downregulated in the mutant. : This study, using the DEAPR strategy, clearly demonstrates the dramatic changes associated with two seemingly similar mutations, suggesting the deployment of different treatment strategies based on the type of mutation present.
约10%的急性髓系白血病（AML）患者存在突变，其中近一半发生在密码子12处，但对于不同的G12突变体如何影响癌细胞活性知之甚少。：一种新的生物信息学技术，差异表达和通路排序（DEAPR），用于比较含有突变的AML THP-1细胞与B11细胞（去除了等位基因并引入了多西环素诱导型等位基因的THP-1衍生细胞）时，确定单个基因和相关通路方面最显著的变化。：总共1456个差异表达（DE）的蛋白质编码基因与突变唯一相关，而585个DE蛋白质编码基因是突变特有的。尽管涉及的基因并不都在两个列表中，但先天免疫系统通路在两个突变体特异性列表中都很突出。此外，两个也与先天免疫相关的钙卫蛋白基因（和）在突变体中上调，在突变体中下调。：本研究使用DEAPR策略，清楚地证明了与两种看似相似的突变相关的巨大变化，表明应根据存在的突变类型采用不同的治疗策略。
