Chromosome 15q deletions confer inferior outcomes among children with ETV6::RUNX1 B-cell acute lymphoblastic leukemia

Wang’ondu R, Kairalla JA, Shago M, Angiolillo AL, Breidenbach H, Burke MJ, Carroll AJ, Rabin KR, Salzer WL, Schore RJ, Wang C, Hunger SP, Teachey DT, Raetz EA, Loh ML, Davis KL, Rau RE. Chromosome 15q deletions confer inferior outcomes among children with ETV6::RUNX1 B-cell acute lymphoblastic leukemia. Blood Adv. 2026 Jun 23;10(12):4109-4112. doi: 10.1182/bloodadvances.2026019599. PMID: 41985005; PMCID: PMC13263678.

Present in ∼25% of childhood B-cell acute lymphoblastic leukemia (B-ALL), the ETV6::RUNX1 fusion resulting from t(12;21)(p13;q22) constitutes one of the most frequent genetic subtypes of pediatric B-ALL. Outcomes for patients with ETV6::RUNX1 are excellent with risk-adapted chemotherapy regimens and are further improved with the addition of blinatumomab.1, 2, 3, 4 Yet, some patients with ETV6::RUNX1 leukemia relapse following chemotherapy, representing a high proportion of late relapses; thus, refined risk-stratification strategies are needed.5, 6, 7 Studies of patients with ETV6::RUNX1 B-ALL treated on various clinical trials have identified potential genomic modifiers of risk, including segmental chromosomal deletions.8, 9, 10, 11 In a relapse-enriched case-control analysis of patients treated on Children’s Oncology Group (COG) trials, unbalanced chromosome 21 translocations (resulting in ETV6::RUNX1 or RUNX1 gain) and 15q deletions, ranging from 8.4 kb to whole-chromosome loss (average of 3.7 Mb), involving the INO80 gene (15q15.1), were linked to increased risk of relapse.11 Conversely, patients with ETV6::RUNX1 and 11q deletions, frequently including KMT2A, had a lower likelihood of relapse.11 We evaluated these prognostic modifiers in 1580 patients with National Cancer Institute (NCI) standard-risk (SR) ETV6::RUNX1 B-ALL treated on COG trials AALL0932 and AALL1131.