This once again suggests a mechanism in which individuals with CH who are exposed to cytotoxic therapy have a positive selection of clones containing TP53 and other DNA damage response (DDR) gene variants, which subsequently attain clonal dominance and acquisition of additional somatic variants, driving the development of aggressive and treatment-resistant t-MNs with higher prevalence of TP53 variants and complex karyotype. Here, TP53 is linked to cyclic hematopoiesis.