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

Bendik Lund; Agata Wesolowska-Andersen; Birgitte Lausen; Louise Borst; Kirsten Kørup Rasmussen; Klaus Müller; Helge Klungland; Ramneek Gupta; Kjeld Schmiegelow

doi:10.1111/ejh.12243

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

Bendik Lund, Agata Wesolowska-Andersen, Birgitte Lausen, Louise Borst, Kirsten Kørup Rasmussen, Klaus Müller, Helge Klungland, Ramneek Gupta, Kjeld Schmiegelow

Research output: Contribution to journal › Journal article › Research › peer-review

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.

Original language	English
Journal	European Journal of Haematology
Volume	92
Issue number	4
Pages (from-to)	321-330
ISSN	0902-4441
DOIs	https://doi.org/10.1111/ejh.12243
Publication status	Published - 2014

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{18f86ac3455a4e6eb85649805281509e,

title = "Host genome variations and risk of infections during induction treatment for childhood acute lymphoblastic leukaemia",

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 {\textquoteleft}G-protein-coupled receptor (GPCR) downstream signalling{\textquoteright}, {\textquoteleft}Bile acid and bile salt metabolism{\textquoteright} and {\textquoteleft}Class I MHC-mediated antigen processing and presentation{\textquoteright} 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.",

keywords = "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",

author = "Bendik Lund and Agata Wesolowska-Andersen and Birgitte Lausen and Louise Borst and Rasmussen, {Kirsten K{\o}rup} and Klaus M{\"u}ller and Helge Klungland and Ramneek Gupta and Kjeld Schmiegelow",

year = "2014",

doi = "10.1111/ejh.12243",

language = "English",

volume = "92",

pages = "321--330",

journal = "European Journal of Haematology",

issn = "0902-4441",

publisher = "Wiley-Blackwell",

number = "4",

}

TY - JOUR

T1 - Host genome variations and risk of infections during induction treatment for childhood acute lymphoblastic leukaemia

AU - Lund, Bendik

AU - Wesolowska-Andersen, Agata

AU - Lausen, Birgitte

AU - Borst, Louise

AU - Rasmussen, Kirsten Kørup

AU - Müller, Klaus

AU - Klungland, Helge

AU - Gupta, Ramneek

AU - Schmiegelow, Kjeld

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common female, male

KW - human CBR1 gene [Hominidae] single-nucleotide polymorphism

KW - human CCL11 gene [Hominidae] single-nucleotide polymorphism

KW - human OR51F1 gene [Hominidae] single-nucleotide polymorphism

KW - human POLDIP3 gene [Hominidae] single-nucleotide polymorphism

KW - bile salt metabolism

KW - 03502, Genetics - General

KW - 03508, Genetics - Human

KW - 14004, Digestive system - Physiology and biochemistry

KW - 15006, Blood - Blood, lymphatic and reticuloendothelial pathologies

KW - 24004, Neoplasms - Pathology, clinical aspects and systemic effects

KW - 24010, Neoplasms - Blood and reticuloendothelial neoplasms

KW - 34508, Immunology - Immunopathology, tissue immunology

KW - 36001, Medical and clinical microbiology - General and methods

KW - Clinical Immunology

KW - Hematology

KW - Infection

KW - Molecular Genetics

KW - Oncology

KW - genome variation

KW - infection Infection (MeSH) infectious disease

KW - lymphoblastic leukemia Leukemia, Lymphocytic (MeSH) neoplastic disease, immune system disease, blood and lymphatic disease

KW - Biochemistry and Molecular Biophysics

KW - Human Medicine, Medical Sciences

KW - bile acid digestive system

KW - blood culture clinical techniques, diagnostic techniques

KW - HEMATOLOGY

KW - BURROWS-WHEELER TRANSFORM

KW - ACUTE MYELOID-LEUKEMIA

KW - PEDIATRIC-PATIENTS

KW - READ ALIGNMENT

KW - CHILDREN

KW - CHEMOTHERAPY

KW - THERAPY

KW - ASSOCIATION

KW - CANCER

KW - POLYMORPHISMS

KW - immunogenetics

KW - single-nucleotide polymorphisms

KW - pharmacogenetics

KW - infection

KW - childhood leukaemia

KW - G protein coupled receptors

KW - Childhood leukaemia

KW - Immunogenetics

KW - Pharmacogenetics

KW - Single-nucleotide polymorphisms

U2 - 10.1111/ejh.12243

DO - 10.1111/ejh.12243

M3 - Journal article

C2 - 24330153

SN - 0902-4441

VL - 92

SP - 321

EP - 330

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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