Evolving heterogeneity in acute lymphoblastic leukemia

Abstract

Despite high survival rates for children with acute lymphoblastic leukemia (ALL) only 40% of adult patients will achieve long-term disease-free survival, and relapses in both pediatric and adult ALL are often fatal. In 50% of patients the clones present at relapse are not the dominant clone at diagnosis but have evolved from an ancestral pre-leukemic clone. In order to investigate the functional consequences of clonal evolution in disease progression and therapy resistance we performed in depth genomic and functional analysis of 14 paired diagnosis/relapse samples from adult and pediatric B-ALL patients with varying cytogenetics.