TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort

Abstract

The effect of TP53 alterations on childhood B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. To investigate the impact of TP53 deletion (TP53^del) and TP53 mutation (TP53^mut) on prognosis, this post-hoc study used fluorescence in situ hybridization test to detect TP53^del in 914 newly diagnosed B-ALL children from a prospective Chinese Children’s Cancer Group ALL-2015 cohort. Targeted gene sequencing was used to identify TP53^mut in 345 out of the 914 patients. TP53^del was detected in 4.4% of cases. The frequency of hypodiploidy was higher in TP53^del subgroup (7.5% vs. 0.5%, P = 0.002), but patients with TP53^del were less likely to have other recurrent genetic abnormalities, including BCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and MLL rearrangement. Univariable and multivariable analyses indicated that TP53^del was an independent risk factor for overall and disease-free survival. Furthermore, stratification analysis revealed that TP53^del was associated with adverse outcomes in patients with positive MRD after induction (0.0% vs. 58.2%, P < 0.001), suggesting an MRD-dependent pattern. But TP53^mut was not associated with poor survival (79.2% vs. 85.3%, P = 0.317). In summary, TP53^del may serve as a predictor for poor prognosis in pediatric B-ALL. Especially children in intermediate-risk group with positive MRD and TP53^del may deserve more aggressive treatment.