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Background  Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as  MLL  rearrangements ( MLL -r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of  IKZF1 ,  ARID5B , and  CEBPE  could be related to the onset of EAL cases (<24 months-old at diagnosis).    Methods  The SNPs ( IKZF1  rs11978267,  ARID5B  rs10821936 and rs10994982,  CEBPE  rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI).    Results  Children with the  IKZF1  SNP had an increased risk of developing  MLL -germline ALL in white children. The heterozygous/mutant genotype in  ARID5B  rs10994982 significantly increased the risk for  MLL -germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in  ARID5B  rs10821936 increased the risk for  MLL -r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore,  ARID5B  rs10821936 conferred increased risk for  MLL - MLLT3  positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that  CEBPE  rs2239633 confers increased genetic susceptibility to EAL.    Conclusions   IKZF1  and  CEBPE  variants seem to play a minor role in genetic susceptibility to EAL, while  ARID5B  rs10821936 increased the risk of  MLL-MLLT3 . This result shows that genetic susceptibility could be associated with the differences regarding  MLL  breakpoints and partner genes.

ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia