<p>In this issue of , Gu and colleagues developed a mouse model of myeloproliferative neoplasm driven by and , which cooperated to induce malignant transformation and metabolic reprogramming of leukemic stem cells at least in part through loss of normal epigenetic regulation of gene expression. Furthermore, their findings point to and branched chain amino acid metabolism as biological dependencies and potential therapeutic targets in myeloid neoplasms..</p>