Volume 10 Number 2 2026
The exposome and genomic susceptibility in childhood acute lymphoblastic leukaemia
Naif Saad Alsuwayti 1, Meshari Farzal Ashwi Alshammari 2, Rasoul Pourhakimrezaei 3, Mohammad Javad Mousavi 4, Widia Sari 5
Integrative Biomedical Research 10 (2) 1-8 https://doi.org/10.25163/biomedical.10210966
Submitted: 01 May 2026 Revised: 20 June 2026 Accepted: 30 June 2026 Published: 02 July 2026
Childhood leukaemia is the commonest cancer of childhood, yet for most children who develop it we still cannot say why. Established, non-modifiable factors account for fewer than one in ten cases, and incidence appears to be edging upward, which points, however indirectly, at the environment. This review asks what the exposome framework, set against modern cancer genomics, can add. We synthesised recent epidemiological, toxicological and whole-genome sequencing evidence on acute lymphoblastic leukaemia (ALL), organising it around the two-hit developmental model in which a prenatal initiating lesion is followed by postnatal secondary hits. Backtracking studies place the first hit firmly in utero: the ETV6::RUNX1 fusion can be recovered from banked cord blood, mostly in CD34? B-cell progenitors, although only a small fraction of these clones ever become clinical disease. The external exposome supplies plausible triggers for the second hit. Neonatal concentrations of the PFAS derivatives MeFOSAA and EtFOSAA, residential proximity to vineyards and barley, fine particulate matter (a hazard ratio near 1.40 per 5 µg/m³), proximity to power lines, gestational heat and a late-summer diagnostic peak have each been linked to risk, though effect sizes are modest and confidence intervals often wide. On the internal side, germline variants at CDKN2A/2B, IKZF1, ARID5B and CEBPE interact epistatically, and somatic mutational signatures, APOBEC, oxidative SBS18 and RAG-mediated SV7, read almost like forensic traces of specific exposures. Integrating these layers may eventually support prevention and early interception, but the evidence, while suggestive, is not yet strong enough to guide policy on its own.
Keywords: childhood leukaemia; acute lymphoblastic leukaemia; exposome; environmental exposures; germline susceptibility; mutational signatures; cancer prevention
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