Author(s)

Kyu-Tae Kim, David Mossman, Donald Small, Rodney J. Scott

Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, New Lambton, Australia.
School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia.
School of Medicine, Johns Hopkins University, Baltimore, USA.

The pyrimidine analog, 5-aza-2’-deoxycytidine (5-aza-dC) is a DNA methyltransferase inhibitor that triggers DNA demethylation leading to the reactivation of epigenetically silenced tumor suppressor genes. To understand the shift in gene expression which mediates the beneficial 5-aza-dC effects in leukemia, we have treated human myeloid derived leukemic cells with 5-aza-dC. Target genes were identified first in MV4-11 cells using a genome-wide gene expression profiling assay to detect differences in treated and untreated cells. From this analysis six genes were identified (HOXA4, HOXD4, HOXA8, HOXD12, CD9 and RGS2) as being significantly different expressed after treatment. To validate microarray data, we performed quantitative PCR on these genes from multiple leukemic cells. The results suggest that these genes are epigenetically regulated indicating that dysregulation of HOXA4, HOXD4, HOXA8, HOXD12, CD9 and RGS2 expression may play an important role in establishing the malignant phenotype in AML.

5-Aza-2’-deoxycytidine; Gene Expression Profile; HOX; CD9; RGS2

K. Kim, D. Mossman, D. Small and R. J. Scott, "Gene Expression Profiling of Human Myeloid Leukemic MV4-11 Cells Treated with 5-Aza-2’-deoxycytidine," Journal of Cancer Therapy, Vol. 3 No. 3, 2012, pp. 177-182. doi: 10.4236/jct.2012.33025.