Histone modification
enzymes regulate gene expression by altering the accessibility of promoters to
transcription factors. We sought to determine whether the genes encoding
histone modification
enzymes are dysregulated in pediatric
acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding
histone modification
enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls. The expression profile of
histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls. Eleven genes were upregulated in pediatric ALL, including the
histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative
tumor suppressor EP300. Future studies will seek to determine whether these genes serve as
biomarkers of pediatric ALL. Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35). Ingenuity Pathway Analysis also indicated that
curcumin and miR-34 are upstream regulators of
histone-modifying
enzymes; future studies will seek to validate these results and examine the role of
curcumin and miR-34 in
leukemia. This study provides new clues into the molecular mechanisms of pediatric ALL.