Document Detail


Genetic variants modify susceptibility to leukemia in infants: a Children's Oncology Group report.
MedLine Citation:
PMID:  22422485     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The mixed lineage leukemia (MLL) gene is commonly rearranged in infant leukemia (IL). Genetic determinants of susceptibility to IL are unknown. Recent genome-wide association studies for childhood acute lymphoblastic leukemia (ALL) have identified susceptibility loci at IKZF1, ARID5B, and CEBPE.
PROCEDURE: We genotyped these loci in 171 infants with leukemia and 384 controls and evaluated associations overall, by subtype [ALL, acute myeloid leukemia (AML)], and by presence (+) or absence (-) of MLL rearrangements.
RESULTS: Homozygosity for a variant IKZF1 allele (rs11978267) increased risk of infant AML [Odds ratio (OR) = 3.9, 95% confidence interval (CI) = 1.8-8.4]; the increased risk was similar for AML/MLL+ and MLL- cases. In contrast, risk of ALL/MLL- was increased in infants homozygous for the IKZF1 variant (OR = 5.1, 95% CI = 1.8-14.5) but the variant did not modify risk of ALL/MLL+. For ARID5B (rs10821936), homozygosity for the variant allele increased risk for the ALL/MLL- subgroup only (OR = 7.2, 95% CI = 2.5-20.6). There was little evidence of an association with the CEBP variant (rs2239633).
CONCLUSION: IKZF1 is expressed in early hematopoiesis, including precursor myeloid cells. Our data provide the first evidence that IKZF1 modifies susceptibility to infant AML, irrespective of MLL rearrangements, and could provide important new etiologic insights into this rare and heterogeneous hematopoietic malignancy.
Authors:
Julie A Ross; Amy M Linabery; Crystal N Blommer; Erica K Langer; Logan G Spector; Joanne M Hilden; Nyla A Heerema; Gretchen A Radloff; Richard L Tower; Stella M Davies
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-15
Journal Detail:
Title:  Pediatric blood & cancer     Volume:  60     ISSN:  1545-5017     ISO Abbreviation:  Pediatr Blood Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-03-07     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  101186624     Medline TA:  Pediatr Blood Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31-4     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Child
Genetic Predisposition to Disease*
Humans
Ikaros Transcription Factor / genetics
Leukemia, Myeloid, Acute / genetics*
Myeloid-Lymphoid Leukemia Protein / genetics
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Grant Support
ID/Acronym/Agency:
K05 CA157439/CA/NCI NIH HHS; K05 CA157439/CA/NCI NIH HHS; K05 CA157439-01/CA/NCI NIH HHS; R01 CA079940/CA/NCI NIH HHS; R01 CA079940/CA/NCI NIH HHS; R01 CA079940-08/CA/NCI NIH HHS; T32 CA099936/CA/NCI NIH HHS; T32 CA099936/CA/NCI NIH HHS; T32 CA099936-09/CA/NCI NIH HHS; U10 CA013539/CA/NCI NIH HHS; U10 CA098543/CA/NCI NIH HHS; U10CA13539/CA/NCI NIH HHS; U10CA98543/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/IKZF1 protein, human; 0/MLL protein, human; 148971-36-2/Ikaros Transcription Factor; 149025-06-9/Myeloid-Lymphoid Leukemia Protein
Comments/Corrections

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