While significant progress has been made in elucidating the coding mutational profile of JMML, the contribution of the non-coding genome to the pathogenesis of the disease remains mostly unexplored.

Enhancers are crucial non-coding regulatory DNA elements, which physically interact with the promoters of their target genes, boosting their expression. Several examples illustrate how enhancer amplification/deletion, de novo enhancer generation, or mutation-driven enhancer activation/inactivation can contribute to the pathogenesis of different types of leukemia. However, the exploration of aberrant enhancer function in JMML remains an uncharted territory.

This project endeavors to unravel the enhancer landscape of JMML, shedding light on abnormal enhancer functions that play a pivotal role in the disease. Leveraging genomics, bioinformatics, and functional approaches, the project aims to broaden our comprehension of previously overlooked mechanisms contributing to the initiation and progression of JMML. By doing so, it strives to pave the way for a more comprehensive understanding of this intricate disease.