{"title":"携带FLT3-ITD突变的AML患者N-MYC癌基因表达的变化","authors":"Konstantin Bogdanov, Ekaterina Kudryavtseva, Yulia Fomicheva, Irina Churkina, Elza Lomaia, Larisa Girshova, Yuri Osipov, Andrey Zaritskey","doi":"10.3390/pathophysiology30030024","DOIUrl":null,"url":null,"abstract":"<p><p>Mutations in the <i>FLT3</i> gene not only lead to abnormalities in its structure and function, but also affect the expression of other genes involved in leukemogenesis. This study evaluated the expression of genes that are more characteristic of neuroblastoma but less studied in leukemia. <i>N-MYC</i> oncogene expression was found to be more than 3-fold higher in primary AML patients carrying the <i>FLT3-ITD</i> mutation compared to carriers of other mutations as well as patients with normal karyotype (<i>p</i> = 0.03946). In contrast to the expression of several genes (<i>C-MYC</i>, <i>SPT16</i>, <i>AURKA</i>, <i>AURKB</i>) directly correlated to the allelic load of <i>FLT3-ITD</i>, the expression of the <i>N-MYC</i> oncogene is extremely weakly related or independent of it (<i>p</i> = 0.0405). Monitoring of <i>N-MYC</i> expression in some patients with high <i>FLT3-ITD</i> allelic load receiving therapy showed that a decrease in <i>FLT3-ITD</i> allelic load is not always accompanied by a decrease in <i>N-MYC</i> expression. On the contrary, <i>N-MYC</i> expression may remain elevated during the first three months after therapy, which is additional evidence of the emergence of resistance to therapy and progression of AML.</p>","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":"30 3","pages":"296-313"},"PeriodicalIF":2.7000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443239/pdf/","citationCount":"0","resultStr":"{\"title\":\"Shift of N-MYC Oncogene Expression in AML Patients Carrying the FLT3-ITD Mutation.\",\"authors\":\"Konstantin Bogdanov, Ekaterina Kudryavtseva, Yulia Fomicheva, Irina Churkina, Elza Lomaia, Larisa Girshova, Yuri Osipov, Andrey Zaritskey\",\"doi\":\"10.3390/pathophysiology30030024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mutations in the <i>FLT3</i> gene not only lead to abnormalities in its structure and function, but also affect the expression of other genes involved in leukemogenesis. This study evaluated the expression of genes that are more characteristic of neuroblastoma but less studied in leukemia. <i>N-MYC</i> oncogene expression was found to be more than 3-fold higher in primary AML patients carrying the <i>FLT3-ITD</i> mutation compared to carriers of other mutations as well as patients with normal karyotype (<i>p</i> = 0.03946). In contrast to the expression of several genes (<i>C-MYC</i>, <i>SPT16</i>, <i>AURKA</i>, <i>AURKB</i>) directly correlated to the allelic load of <i>FLT3-ITD</i>, the expression of the <i>N-MYC</i> oncogene is extremely weakly related or independent of it (<i>p</i> = 0.0405). Monitoring of <i>N-MYC</i> expression in some patients with high <i>FLT3-ITD</i> allelic load receiving therapy showed that a decrease in <i>FLT3-ITD</i> allelic load is not always accompanied by a decrease in <i>N-MYC</i> expression. On the contrary, <i>N-MYC</i> expression may remain elevated during the first three months after therapy, which is additional evidence of the emergence of resistance to therapy and progression of AML.</p>\",\"PeriodicalId\":19852,\"journal\":{\"name\":\"Pathophysiology\",\"volume\":\"30 3\",\"pages\":\"296-313\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443239/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pathophysiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/pathophysiology30030024\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathophysiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/pathophysiology30030024","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
Shift of N-MYC Oncogene Expression in AML Patients Carrying the FLT3-ITD Mutation.
Mutations in the FLT3 gene not only lead to abnormalities in its structure and function, but also affect the expression of other genes involved in leukemogenesis. This study evaluated the expression of genes that are more characteristic of neuroblastoma but less studied in leukemia. N-MYC oncogene expression was found to be more than 3-fold higher in primary AML patients carrying the FLT3-ITD mutation compared to carriers of other mutations as well as patients with normal karyotype (p = 0.03946). In contrast to the expression of several genes (C-MYC, SPT16, AURKA, AURKB) directly correlated to the allelic load of FLT3-ITD, the expression of the N-MYC oncogene is extremely weakly related or independent of it (p = 0.0405). Monitoring of N-MYC expression in some patients with high FLT3-ITD allelic load receiving therapy showed that a decrease in FLT3-ITD allelic load is not always accompanied by a decrease in N-MYC expression. On the contrary, N-MYC expression may remain elevated during the first three months after therapy, which is additional evidence of the emergence of resistance to therapy and progression of AML.
期刊介绍:
Pathophysiology is an international journal which publishes papers in English which address the etiology, development, and elimination of pathological processes. Contributions on the basic mechanisms underlying these processes, model systems and interdisciplinary approaches are strongly encouraged.