Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype–genotype study

Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well‐known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL‐2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome‐8‐Bead chip) aged 1–45 years, diagnosed with B‐cell precursor (BCP‐) or T‐cell ALL (T‐ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC‐associated germline genetic variants in a genome‐wide association study (GWAS) while adjusting for age and ALL subtype associations. Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (ρBCP‐ALL = −.17, ρT‐ALL = −.19; p