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

  • 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.

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  • Additional file 1: Table S1: Demographic and biological characteristics of controls and cases according to age at diagnosis.

  • Additional file 2: Table S2: The distribution of allele frequencies among controls and cases within the major acute leukemia subtypes, Brazil, 2003-2013.

  • Additional file 3: Table S3: The distribution of allele frequencies among controls and cases within the two major acute leukemia subtypes by skin colour and by MLL gene status, Brazil, 2003-2013.

  • Additional file 4: Table S4.: The risk associations between genetic variants and MLL status in overall and specific subtypes of acute leukemia, Brazil, 2003-2013.

  • Additional file 5: Table S5: Cumulative risk effects of IKZF1, ARID5B and CEBPE genetic variants according to leukemia subtype and MLL status, Brazil, 2003-2013.

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Author:Mariana Emerenciano, Thayana Conceição Barbosa, Bruno Almeida Lopes, Caroline Barbieri Blunck, Alessandra Faro, Camilla Andrade, Claus Meyer, Rolf MarschalekORCiDGND, Maria S. Pombo-de-OliveiraORCiD
Parent Title (English):BMC cancer
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Date of Publication (online):2014/02/25
Date of first Publication:2014/02/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:The Brazilian Collaborative Study Group of Infant Acute Leukemia
Release Date:2014/04/09
Tag:ARID5B; CEBPE; IKZF1; Infant leukemia; MLL
Page Number:7
© 2014 Emerenciano et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Medizin / Medizin
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 2.0