Changes in expression of WT1 during induced differentiation of the acute myeloid leukemia cell lines by treatment with 5-aza-2′-deoxycytidine and all-trans retinoic acid

摘要

The aim of the present study was to investigate the effect of 5-aza-2′-deoxycytidine (decitabine; DAC) and all-trans retinoic acid (ATRA) on Wilms' tumor 1 (WT1) in acute myeloid leukemia (AML) in vitro. The methylation status of the WT1 promoter was analyzed using methylation-specific polymerase chain reaction (MSP). The expression level of WT1 was detected by reverse transcription-quantitative polymerase chain reaction. The effect of DAC and ATRA on cell differentiation was evaluated by flow cytometry. The WT1 gene was methylated in U937 cells, but unmethylated in SHI-1 and K562 cells; the U937 cells did not express the WT1 gene, but the SHI-1 and K562 cells highly expressed the WT1 gene. DAC and ATRA, alone or in combination, exhibited no effect on the expression level of WT1 in the U937 cells and on the differentiation of the K562 cells. The combined treatment of DAC and ATRA markedly decreased the WT1 expression levels of the SHI-1 and K562 cells, and induced the differentiation of the SHI-1 and U937 cells. In the SHI-1 cells, WT1 expression changed inversely to the dynamic changes of cluster of differentiation 11b-positive rates. In conclusion, the combined treatment of DAC and ATRA has clinical therapeutic potential in acute monocytic leukemia patients with high WT1 expression and a poor response to standard induction chemotherapy.