Abstract
Abstract 3614
Pediatric MLL-rearranged acute monoblastic leukemia with t(9;11)(p22;q23) has a good outcome as compared to other MLL-rearranged AML. The biological background for this difference is unknown. Therefore, we compared gene expression profiles (GEP) of -t(9;11)(p22;q23) patients with other MLL-rearranged AML patients to identify differentially expressed genes.
We performed GEP (Affymetrix HG U133 plus 2.0) in 245 pediatric AML patients (237 de novo and 8 secondary AML patients) and used RT-qPCR and Western Blot to validate expression. Methylation specific PCR was used to investigate epigenetic regulation. We tested the effect of the demethylating agent decitabine and the effect of knock-down by siRNA on both proliferation and drug sensitivity in AML cell lines.
IGSF4, a cell-cell adhesion molecule, was highly expressed in AML-t(9;11). Expression within AML-t(9;11) was 18.5 times higher in FAB-M5 versus other FAB-types (p=0.013). RT-qPCR and Western Blot confirmed this. Methylation status investigation showed that high IGSF4 expressing AML-t(9;11) patients with FAB-M5 have no promoter hypermethylation, whereas all other cases do. This was also seen in cell lines. Cell line incubation with decitabine resulted in promoter demethylation and increased expression of IGSF4. Downregulation of IGSF4 by siRNA did not affect proliferation nor drug sensitivity in suspension culture.
In conclusion, we identified IGSF4 overexpression to be discriminative for AML-t(9;11) with FAB-M5, regulated partially by promoter methylation.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
