A20: New Possible Targetable Genes For Future Treatment of MLL Leukemias
1International Burch University, Sarajevo, Bosnia and Herzegovina
Background: MLL leukemias (mixed lineage leukemia) have unique clinical and biological characteristics. MLL partners with over 50 different genes that result in the expression of chimeric proteins.The chromosomal translocations t(9;11), t(11;19) and t(4;11) leading respectively to MLL-AF9, MLL-ENL and MLL-AF4 fusions are the most frequent.
Methods: Using the whole genome profiling of patient samples with acute myeloid leukemia (AMLs), we analysed the differential gene expression, methylation pattern, and mutational spectra between MLL and other AML types (n=197) .
Results: We found that 120 genes were differentially expressed, where 36 genes had more than 2 fold expression difference including HOXA9, CFH, DDX4, MSH4, MSMB, TWIST1, ZSWIM2, POU6F2 and others. Since we analysed expression from patient samples, we further compared the candidate genes to common MLL cell lines. Our results show that most genes did not show the same expression pattern in patients and in corresponding MLL cell lines.
Since rearrangements of MLL gene lead to aberrant methylation, we investigated the differential methylation patterns between MLL and other AML types and identified affected methylation hotspots. The methylation loci were categorized into two groups: group one (between 5 and 9 fold difference) and group two (>10 fold difference). In the second group, 14 locations in 9 genes were found including RAET1E, HSD17B2, RNASE11, DGK1, POU6F2, NAGS, PIK3C2G, GADL1, and KRT13.
Conclusions: MLL leukemias exhibit unique clinical and biological phenotype. Our results point to new possible targetable genes for future treatment of MLL leukemias.