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-Oliveira
URN:urn:nbn:de:hebis:30:3-333949
DOI:https://doi.org/10.1186/1471-2407-14-127
ISSN:1471-2407
Parent Title (English):BMC cancer
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
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
Volume:14
Issue:127
Page Number:7
Note:
© 2014 Emerenciano et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
HeBIS-PPN:364414448
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
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0