Chronic Neutrophilic Leukemia (CNL) is a myeloproliferative neoplasm characterized by an overproduction of mature neutrophils. In over 90% of CNL cases, patients present with a mutation in Colony Stimulating Factor 3 Receptor (CSF3R), a receptor that plays a prominent role in proliferation and differentiation of neutrophils. When mutated, this receptor is aberrantly activated, leading to enhanced downstream signaling. A majority of these patients also harbor a mutation in Additional Sex-Combs Like 1 (ASXL1), an epigenetic regulator of hematopoiesis, leading to disrupted hematologic gene regulation. The combination of those mutations confers poor prognosis. In this study, we used transgenic mouse models to determine the role of ASXL1 mutations in the pathogenesis of CSF3R-mutant CNL.