Research

Host genome variations and risk of infections during induction treatment for childhood acute lymphoblastic leukaemia

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Abstract

Objectives: To investigate association of host genomic variation and risk of infections during treatment for childhood acute lymphoblastic leukaemia (ALL). Methods: We explored association of 34 000 singlenucleotide polymorphisms (SNPs) related primarily to pharmacogenomics and immune function to risk of infections among 69 ALL patients on induction therapy. Results: Forty-eight (70%) patients experienced infectious events including 23 with positive blood cultures. Infectious events and positive blood cultures were associated significantly with 24 and 21 SNPs, respectively (P < 0.01). Classification and regression tree analysis demonstrated rs11033797 (OR51F1), rs2835265 (CBR1), rs28627172 (POLDIP3) and rs1129844 (CCL11) to be predictive of outcome. Among 61 patients for whom read-outs were available for all four SNPs, 40 of 41 patients with the worst SNP profile experienced at least one infectious event compared with five of the remaining 20 patients (Hazard ratio 9.0, 95% CI 3.4–23.5, which was unchanged after adjustments for neutrophil counts). Pathway analysis identified variations in ‘G-protein-coupled receptor (GPCR) downstream signalling’, ‘Bile acid and bile salt metabolism’ and ‘Class I MHC-mediated antigen processing and presentation’ to be highly predictive of infections. Conclusions: Our data indicate that host genomic profiling may predict the risk of infections during induction therapy. This may facilitate development of individualised supportive care.

Primates Mammalia Vertebrata Chordata Animalia (Animals Chordates Humans Mammals Primates Vertebrates) - Hominidae [86215] human common female male human CBR1 gene [Hominidae] single-nucleotide polymorphism human CCL11 gene [Hominidae] single-nucleotide polymorphism human OR51F1 gene [Hominidae] single-nucleotide polymorphism human POLDIP3 gene [Hominidae] single-nucleotide polymorphism bile salt metabolism 03502 Genetics - General 03508 Genetics - Human 14004 Digestive system - Physiology and biochemistry 15006 Blood - Blood lymphatic and reticuloendothelial pathologies 24004 Neoplasms - Pathology clinical aspects and systemic effects 24010 Neoplasms - Blood and reticuloendothelial neoplasms 34508 Immunology - Immunopathology tissue immunology 36001 Medical and clinical microbiology - General and methods Clinical Immunology Hematology Infection Molecular Genetics Oncology genome variation infection Infection (MeSH) infectious disease lymphoblastic leukemia Leukemia Lymphocytic (MeSH) neoplastic disease immune system disease blood and lymphatic disease Biochemistry and Molecular Biophysics Human Medicine Medical Sciences bile acid digestive system blood culture clinical techniques diagnostic techniques HEMATOLOGY BURROWS-WHEELER TRANSFORM ACUTE MYELOID-LEUKEMIA PEDIATRIC-PATIENTS READ ALIGNMENT CHILDREN CHEMOTHERAPY THERAPY ASSOCIATION CANCER POLYMORPHISMS immunogenetics single-nucleotide polymorphisms pharmacogenetics infection childhood leukaemia G protein coupled receptors Childhood leukaemia Immunogenetics Pharmacogenetics Single-nucleotide polymorphisms