We show that asxl1 is important for the survival of newly formed hematopoietic stem and progenitor cells (HSPCs) as they migrate into the caudal hematopoietic tissue of the zebrafish embryo, and that homozygous loss of asxl1 induces mitochondrial apoptosis of HSPCs through the activation of bim and bid. In fish with heterozygous asxl1 inactivation, half of the 5-month-old adults exhibited MPN. Here, BCL2L11 is linked to myeloproliferative disorder.