The Clinical and Genetic Features of ETV6/RUNX1-like Acute Lymphoblastic Leukemia in Pediatric: A Multicenter Retrospective Study

Abstract The clinical-genetic characteristics of ETV6-RUNX1-like acute lymphoblastic leukemia (ALL) is still unclear in pediatrics. Therefore, we conducted Fluorescent In Situ Hybridization (FISH), Polymerase Chain Reaction(PCR) and Whole Transcriptome Sequencing (WTS) on 2171 B-lineage ALL cases and identified 49 (2.3%) ETV6-RUNX1-like and 406 (18.7%) ETV6-RUNX1 cases. We found that: i) ETV6-RUNX1-like patients were characterized by ETV6 abnormalities and enrich for PAX5, KRAS, CDKN2A/2B, CRLF2, IKZF1, PTTN11, NRAS, FLT3. ii) Genes affecting of transcription factor regulation, RAS signal pathway, cell cycle regulation, JAK/STAT signal pathway and epigenetic modification were significantly frequent in ETV6-RUNX1-like ALL. iii) Four hub genes, ETV6, CDKN2A, ABL1 and MYC, were identified among ETV6-RUNX1-like ALL. The clinical characteristics highlighted that: i) ETV6-RUNX1-like patients had higher minimal residual disease (MRD) persistence at day 15 (D15 MRD) than ETV6-RUNX1 patients (P = 0.023). ii) 5-year event-free survival (EFS) and overall survival (OS) of ETV6-RUNX1-like patients were both significantly worse than ETV6-RUNX1 patients (65.8 ± 15.4% vs. 95.7 ± 1.0%, P < 0.001 and 91.3 ± 4.2% vs 98.2 ± 0.7%, P = 0.006). iii) ETV6-RUNX1-like positive was the risk factor for EFS (HR 3.25 (95% CI, 1.23–8.61); P = 0.018). Therefore, it is important to discern ETV6-RUNX1-like patients early and opt for more intensive chemotherapy for these patients.