Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive hematological malignancy of early childhood. Despite the progress made in elucidating the pathogenesis of JMML, knowledge remains fragmented and the heterogeneity of this disease is still not fully understood. Within this project, we aim to gain a deeper understanding of the interactions between genetic, epigenetic, and transcriptome profiles in JMML by integration of all molecular layers in a cohort of 30 patients. This approach will lead to new insights in disease pathogenesis, a better understanding of its origin and molecular basis, and ultimately to the identification of new therapeutic targets and potential treatments. Moreover, we will particularly focus on the distinct circRNA profile of JMML patients. As circRNAs have some physiological advantages in serving as a biomarker/therapeutic target, we aim to further define the circRNA transcriptome in JMML and functionally characterize the identified circRNAs with biomarker and therapeutic potential.