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Histone modification is dysregulated in various types of cancers, including hematological malignancies. However, the expression profile of histone-modifying enzymes in pediatric acute monoblastic leukemia (AML FAB M5) has not been investigated. In this study, we evaluated the mRNA expression profile of 85 genes that encode enzymes involved in histone-modification in 27 pediatric AML FAB M5 samples by using a novel real-time PCR array. We obtained a gene cluster consisting of a total of 28 genes (15 up-regulated genes and 13 down-regulated genes). This gene signature revealed up-regulated expression of putative oncogenes GCN5L2, SETD8, KDM5C, AURKAand AURKB, and downregulated putative tumor suppressor genes (TSGs) EP300, PRMT3, PRMT8and NOTCH2. We investigated possible biological interactions between differentially expressed genes using ingenuity pathway analysis (IPA) and found 12 significant networks. Among these, gene expression, cancer, and embryonic development showed the highest number of networks with 39 focus molecules and had an associated significance score of 68. Further, Rb, CDKN2C, and E2F1were found to be upstream regulators of histone-modifying enzymes. This study provides additional insights into the molecular pathogenesis of pediatric AML FAB M5. These genes represent interesting targets with potential for diagnostic, prognostic and therapeutic application in pediatric AML patients.

No relevant conflicts of interest to declare.

Objective: MLL gene rearrangement in pediatric acute lymphoblastic leukemia (ALL) was regarded as high risk factor because of the poorer outcome of overall survival(OS). Some reports further proved that patients with MLL/AF4 had the worse outcome than MLL rearranged with other partners. CCLG-ALL2008 protocol has been carried out in China for more than 5 years. However, there was no reports to evaluate its efficiency on pediatric ALL patients with MLL rearrangement. In this study, we analyzed the data of ALL patients to compare the outcome of patients with MLL rearrangement positive and negative treated by CCLG-2008 protocol.