Lee et al. (2021) recently identified a germline risk locus located in an intergenic region between BCL11A and PAPOLG in E2A/PBX1 ALL patients, indicating that the interplay between germline variants and somatic genomic abnormalities determines the specific ALL subtype. The relationship between E2A/PBX1 fusion gene subtype and VZV infection requires further exploration in the future. The gene discussed is PAPOLG; the disease is acute lymphoblastic leukemia.