Deciphering the Clonal Origin of Relapsed Acute Lymphoblastic Leukemia in Children

In this issue of Blood Cancer Discovery, Waanders and colleagues characterize somatic alterations in a large cohort of relapsed pediatric acute lymphoblastic leukemia (ALL). This comprehensive genomic analysis reveals mutations distinctly associated with primary disease versus response to therapy. In the reconstructed clonal evolution scenarios, relapsed leukemic cells propagate from clones already expanded at diagnosis and rarely from unexpanded dormant ancestral clones. The information gleaned through subclonal mutation analysis at diagnosis may help to estimate relapse risk and select therapeutic options with minimal relapse potential. High prevalence of hypermutation patterns among repeatedly relapsing ALL cases suggests that activating antitumor immunity has a potential to benefit this group of patients. See related article by Waanders et al., p. 96.