Transcriptomic comparison of HSPCs obtained from JMML patients with somatic PTPN11 mutations and HSPCs from mutant zebrafish harboring an NS-associated variant of Shp2 suggested common mechanisms of disease initiation in sporadic and syndromic PTPN11-driven JMML. The gene discussed is PTPN11; the disease is juvenile myelomonocytic leukemia.