Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia.

Genomic alterations of are common and associated with adverse clinical features in B-ALL. The relationship between the type of alteration, disease subtype and outcome are incompletely understood. Leukemia subtype and genomic alterations were determined using transcriptome and genomic sequencing and SNP microarray in 688 pediatric patients with B-ALL in St. Jude Total Therapy 15 and 16 studies. alterations were identified in 115 (16.7%) patients, most commonly in (78%) and -rearranged, -like B-ALL (70%). These alterations were associated with 5-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any alteration ( < 0.0001). deletions of exon 4-7 ( = 0.0002), genomic with any deletion ( = 0.006) or with focal deletion ( = 0.0007), and unfavorable genomic subtypes ( < 0.005) were independently adversely prognostic factors. Associations of genomic and exon 4-7 deletions with adverse outcomes were confirmed in an independent cohort. Genomic with any deletion, deletion of exon 4-7, and unfavorable subtype confer increased risk of relapse. The type of alteration, together with the subtype, are informative for risk stratification and predict response in patients with B-ALL.