Aberrant hypomethylation of SALL4 gene is associated with intermediate and poor karyotypes in acute myeloid leukemia

ObjectiveSALL4 gene has been identified to stimulate the expansion of hematopoietic stem cell (HSCs) and enhance the self-renewal of HSCs. Overexpression of SALL4 has been found in several cancers. The present study was aimed to investigate the methylation status of SALL4 promoter region in acute myeloid leukemia (AML).Designs and methodsThe methylation status of SALL4 promoter was analyzed in 84 patients with AML using methylation-specific PCR (MSP) and its clinical significance was evaluated.ResultsAberrant hypomethylation of SALL4 gene, which was correlated with SALL4 expression, was found in 17.8% (15/84) cases. The patients with SALL4 hypomethylation had significantly older age and higher WBCs than those without SALL4 hypomethylation. The incidence of SALL4 hypomethylation was higher in M1 subtype than in M2 and other subtypes (50%, 26% and 6%, respectively, P = 0.001). SALL4 hypomethylation was associated with cytogenetically intermediate and poor groups. Although survival time of the SALL4-hypomethylated AML was shorter than that of SALL4-methylated group (4 months vs 9 months), the difference was not statistically significant (P = 0.356).ConclusionsHypomethylation of SALL4 promoter is a common event and is associated with the intermediate and poor karyotypes in AML.

► SALL4 promoter hypomethylation is correlated with SALL4 expression in AML.
► 17.8% AML patients have aberrant hypomethylation of SALL4 promoter.
► SALL4 hypomethylation is correlated with old age and high WBCs.
► SALL4 hypomethylation is associated with intermediate and poor karyotypes.