Notwithstanding the exact molecular mechanism by which the CSF3R truncation mutants lead to sMDS/AML, two pivotal questions concerning the population dynamics and population genetics of the mutant clones are: (i) whether the CSF3R truncation mutants are present before application of G-CSF, and (ii) whether G-CSF administration increases mutation rate in hematopoietic stem cells with ELANE mutation. Here, CSF3 is linked to spondylometaphyseal dysplasia, Sedaghatian type.