Juvenile myelomonocytic leukemia (JMML) is an aggressive hematologic malignancy with myeloproliferative characteristics that affects young children and is associated with significant morbidity and mortality. Leukemia stem cells (LSCs) have been shown to drive relapse and progression in JMML and include Lin-CD34+CD38-/+ hematopoietic stem cells (HSCs)​14​. We therefore sought to develop cellular immunotherapy against JMML by employing a multi-modal omics strategy, focusing specifically on targeting chemoresistant LSCs