Mutational dynamics of early and late relapsed childhood ALL: rapid clonal expansion and long-term dormancy.

ABSTRACT: Childhood acute lymphoblastic leukemia (cALL) is the most frequent pediatric cancer. Refractory/relapsed cALL presents a survival rate of ∼45% and is still one of the leading causes of death by disease among children. Mechanisms, such as clonal competition and evolutionary adaptation, govern treatment resistance. However, the underlying clonal dynamics leading to multiple relapses and differentiating early (<36 months postdiagnosis) from late relapse events remain elusive. Here, we use an integrative genome-based analysis combined with serial sampling of relapsed tumors (from primary tumor to ≤4 relapse events) from 19 pre-B-cell cALL patients (8 early and 11 late relapses) to assess the fitness of somatic mutations and infer their ancestral relationships. By quantifying both general clona

SUBMITTER: Spinella JF 

PROVIDER: S-EPMC5812325 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature