Various models of disease evolution in CSF3R-T618I–positive myeloid neoplasms. We compare and contrast to CML (Model 1). Nearly all patients with WHO-defined CNL harbor a CSF3R-T618I mutation (Model 2) according to some datasets. These patients may undergo similar pathologic/disease phases as CML and the transition points are associated with additional genetic changes. It is unclear whether CSF3R-T618I–positive aCML is a distinct entity (Model 3) or a disease evolution from CNL (Model 4). A number of oncogenic drivers are possible in aCML (Table 2). Future studies will help clarify the leading model in aCML. HSC indicates hematopoietic stem cell. The yellow lightning symbol depicts the acquisition of somatic mutation(s).