Beyond BCR::ABL1, variants in the epigenetic modulator DNA (cytosine-5)-methyltransferase 3A (DNMT3A), the polycomb group protein additional sex comb-like 1 (ASXL1), runt-related transcription factor 1 (RUNX1) and Tet methylcytosine dioxygenase 2 (TET2) were shown to be associated with therapy failure indicating defective epigenetic DNA regulation in TKI-resistant CML as already described for other myeloproliferative syndromes (12, 49–51). This evidence concerns the gene ABL1 and chronic myelogenous leukemia, BCR-ABL1 positive.