Complex genotype-phenotype relationships shape the response to treatment of down syndrome childhood acute lymphoblastic leukaemia.

ABSTRACT: Extensive genetic and epigenetic variegation has been demonstrated in many malignancies. Importantly, their interplay has the potential to contribute to disease progression and treatment resistance. To shed light on the complex relationships between these different sources of intra-tumour heterogeneity, we explored their relative contributions to the evolutionary dynamics of Acute Lymphoblastic Leukaemia (ALL) in children with Down syndrome, which has particularly poor prognosis. We quantified the tumour propagating potential of genetically distinct sub-clones using serial transplantation assays and SNP-arrays. While most leukaemias were characterized by a single dominant subclone, others were highly heterogeneous. Importantly, we provide clear and direct evidence that genotypes and phenot

SUBMITTER: Lutz C 

PROVIDER: S-EPMC12658182 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature