Genetic and epigenetic studies of pediatric acute leukemia

Genetic and epigenetic analyses of acute lymphoblastic and myeloid leukemias (ALL, AML) have identified pathogenetically important mutations and/or epigenetic changes that have resulted in improved risk stratification and treatment outcome. However, much remains to be elucidated.

We aim to increase our understanding of the leukemogenic process by focusing on: 1) identification of single base substitution mutational signatures associated with the etiology or pathogenesis of pediatric ALL and AML, 2) evaluation of the genetic and epigenetic consequences of acquired uniparental isodisomies in childhood acute leukemia, and 3) ascertainment of which parental chromosomes are retained in ALL and AML with monosomies in order to investigate if retainment or loss of imprinted gene loci on the monosomic chromosomes plays a role in leukemogenesis.

The subprojects are all based on novel ideas that will be addressed by state-of-the art methods such as whole genome sequencing, transcriptome sequencing, whole genome bisulfite sequencing, and chromatin immunoprecipitation sequencing.

In conclusion, our goals are to identify pathogenetically important genetic and epigenetic abnormalities, delineate novel genetic and/or epigenetic subgroups, identify biomarkers of use for risk stratification and targeted therapy, and, ultimately, to improve the survival of children and adolescents with ALL and AML.