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Genetic variants modify susceptibility to leukemia in infants: a Children's Oncology Group report. Pediatr Blood Cancer 2013 Jan;60(1):31-4

Date

03/17/2012

Pubmed ID

22422485

Pubmed Central ID

PMC3381932

DOI

10.1002/pbc.24131

Scopus ID

2-s2.0-84870191690   36 Citations

Abstract

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.

Author List

Ross JA, Linabery AM, Blommer CN, Langer EK, Spector LG, Hilden JM, Heerema NA, Radloff GA, Tower RL, Davies SM

Author

Richard L. Tower MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Child
Genetic Predisposition to Disease
Histone-Lysine N-Methyltransferase
Humans
Ikaros Transcription Factor
Leukemia, Myeloid, Acute
Myeloid-Lymphoid Leukemia Protein
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a