ABSTRACT
BACKGROUND: Some childhood acute lymphoblastic leukaemias (ALL) can be traced back to a prenatal origin, where a virus infection could be involved in the first pre-leukaemic clone development. The DNA virome of 95 children who later developed ALL was characterised from neonatal blood spots (NBS) using unbiased next-generation sequencing (NGS) and compared with the virome of 95 non-ALL controls. METHODS: DNA was individually extracted from the ALL-patients and controls, pooled, randomly amplified and sequenced using the Illumina MiSeq Sequencing System. RESULTS: Virus-like sequences identified in both groups mapped to human endogenous retroviruses and propionibacterium phage, considered a part of the normal microbial flora. Potential pathogens human herpesvirus type 6 (HHV-6) and parvovirus B19 were also identified, but only few samples in both ALL and controls tested positive by PCR follow-up. CONCLUSIONS: Unbiased NGS was employed to search for DNA from potential infectious agents in neonatal samples of children who later developed ALL. Although several viral candidates were identified in the NBS samples, further investigation by PCR suggested that these viruses did not have a major role in ALL development.
Subject(s)
Blood/virology , Infant, Newborn/blood , Neonatal Screening , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Bacteriophages/isolation & purification , Blood Specimen Collection , Contig Mapping , DNA, Viral/blood , Disease Susceptibility , Endogenous Retroviruses/isolation & purification , Endogenous Retroviruses/pathogenicity , Erythema Infectiosum , Female , Herpesvirus 6, Human/isolation & purification , Herpesvirus 6, Human/pathogenicity , Humans , Male , Parvovirus B19, Human/isolation & purification , Parvovirus B19, Human/pathogenicity , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Sampling Studies , Sequence Analysis, DNA , SwedenABSTRACT
BACKGROUND: In search of a proposed viral aetiology of childhood acute lymphoblastic leukaemia (ALL), the common species C adenoviruses were analysed in Guthrie cards. METHODS: Guthrie cards from 243 children who later developed ALL and from 486 matched controls were collected and analysed by nested polymerase chain reaction for the presence of adenovirus DNA. RESULTS: Adenovirus DNA was reliably detected from only two subjects, both of whom developed ALL. CONCLUSION: Adenovirus DNA is detected in Guthrie card samples at too low a frequency to reveal an association between adenovirus and the development of leukaemia.
