未来治疗混合系白血病的新靶向基因

Senol Dogan
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引用次数: 2

摘要

研究目的:白血病有不同的亚型,具有独特的临床和分子特征。MLL(Mixed Lineage Leukemia,混合谱系白血病)是AML和ALL不同的新亚型之一。材料和方法:通过分析MLL和AML类型(n=197)之间的差异基因表达、甲基化模式和突变谱,基因组表征是理解MLL差异的主要关键。结果:根据MLL的基因组特征,筛选出差异表达的114个基因,其中37个是表达变化超过2倍的靶向基因,包括HOXA9、CFH、DDX4、MSH4、MSMB、TWIST1、ZSWIM2、POU6F2。测量异常甲基化是本研究的第二个基因组特征,因为MLL基因的重排导致异常甲基化。甲基化数据在癌症和对照之间进行了比较,因此在MLL和AML类型之间检测到了高甲基化基因。甲基化位点分为两组:≥10倍差异和≥5且≤10倍差异。一些基因高度甲基化不止一个位置,例如;RAET1E、HSD17B2、RNASE11、DGK1、POU6F2、NAGS、PIK3C2G、GADL1和KRT13。此外,体细胞突变分析表明,CFH具有最高的点突变率9,92%。结论:总的来说,MLL的基因组特征表明它不同于AML,并表现出独特的分子和生物学表型,并为未来治疗MLL白血病指出新的可能靶向基因是两个重要的价值。
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New Possible Targetable Genes for Future Treatment of Mixed Lineage Leukemia
Aim of study: Leukemia has different subtypes, which present unique clinical and molecular characteristics. MLL (Mixed Lineage Leukemia) is one of the new different subtypes than AML and ALL. Materials and Methods: Genomic characterization is the main key understanding the differences of MLL by analysis of differential gene expression, methylation patterns and mutational spectra that were compared and analyzed between MLL and AML types (n=197). Results: According to the genomic characterization of MLL, differentially expressed 114 genes were selected and 37 of them targeted genes having more than 2 fold expression change, including HOXA9, CFH, DDX4, MSH4, MSMB, TWIST1, ZSWIM2, POU6F2. To measure the aberrant methylation is the second genomic characterization of this research because the rearrangements of MLL gene leading to aberrant methylation. The methylation data were compared between cancer and control, so high methylated genes have been detected between MLL and AML types. The methylation loci were categorized into two groups: ≥ 10 fold difference and ≥ 5 and ≤ 10 fold difference. Some of the genes high methylated more than one location such as; RAET1E, HSD17B2, RNASE11, DGK1, POU6F2, NAGS, PIK3C2G, GADL1, and KRT13. In addition to that, analysis of somatic mutation gives us that CFH has the highest point mutation 9,92%. Conclusion: Overall, the MLL genomic characterization shows that it is different than AML and exhibits a unique molecular and biological phenotype and point to new possible targetable genes for future treatment of MLL leukemia are two important values.
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