Open Access Highly Accessed Research article

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

Mariana Emerenciano1, Thayana Conceição Barbosa1, Bruno Almeida Lopes1, Caroline Barbieri Blunck1, Alessandra Faro1, Camilla Andrade1, Claus Meyer2, Rolf Marschalek2, Maria S Pombo-de-Oliveira1* and The Brazilian Collaborative Study Group of Infant Acute Leukemia

Author Affiliations

1 Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro/RJ 20231-050, Brasil

2 Institute of Pharmaceutical Biology/ZAFES/Diagnostic Center of Acute Leukemia (DCAL), Goethe-University of Frankfurt, Frankfurt/Main, Germany

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BMC Cancer 2014, 14:127  doi:10.1186/1471-2407-14-127

Published: 25 February 2014



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).


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).


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.


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.

IKZF1; ARID5B; CEBPE; Infant leukemia; MLL