New Possible Targetable Genes for Future Treatment of Mixed Lineage Leukemia

Abstract

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.