Dr Xiaoming Zhong  speaks to ecancer about the genomic determinants of treatment outcome and identification of a new genomic subset of adult acute lymphoblastic leukaemia from the ECOG-ACRIN E1910 randomised phase III trial.

He says that this study delivers the most comprehensive genomic analysis to date of adult B-cell acute lymphoblastic leukemia (B-ALL), profiling 569 newly diagnosed patients from the E1910 trial.

Researchers identified 268 driver genes, major mutated pathways, and a high prevalence of high-risk subtypes.

A newly discovered molecular subgroup CEBP-altered ALL (CEBPalt) was defined by CEBPA/CEBPB deregulation driven by enhancer hijacking and novel genomic rearrangements. This represents a previously unrecognised driver of leukaemogenesis.

The study also uncovered a high rate of clonal haematopoiesis mutations, particularly TP53, enriched in hypodiploid cases.

Dr Zhong highlights that overall, these findings reshape the genomic understanding of adult B-ALL, introduce a novel CEBP-driven subtype, and refine the molecular context in which blinatumomab provides the greatest therapeutic benefit.