The current study examined the promoter activity of an association signal in a 5'-upstream region of the gene encoding CCAAT/enhancer binding protein epsilon (CEBPE) identified from a recent genome-wide association study (GWAS) for complex acute lymphoblastic leukemia (ALL). This follow-up study first compared the activity of reporter constructs with three haplotypes estimated with the rs2239633 and its proximity nucleotide variants in strong linkage. The most frequent haplotype was CTTTTGT (H1), and the second most frequent haplotype consisted of entirely opposite alleles to H1 (TCGCACC, H2). Their luciferase activity revealed the strongest expression with H2 and the weakest with H1. Subsequent analysis revealed that different luciferase activity was found by the single-nucleotide substitution at rs2239632 and rs2239633 (P<0.05). Especially, the difference in luciferase activity between two alleles of rs2239632 corresponded to the difference between H1 and H2. We concluded that rs2239632 could regulate the expression of the CEBPE gene. We suggest a hypothesis that its risk allele (G) might increase the gene product and lead to leukemogenesis. As a result, a person with the allele or the corresponding haplotype might have increased susceptibility to ALL. Further research is warranted to investigate this hypothesis and the underlying mechanisms.