NPM1 and chronic myelogenous leukemia, BCR-ABL1 positive: Despite the advancements in TKI therapies, however, the effectiveness is always short-term in an advanced phase of CML or acute lymphoblastic leukemia (ALL) that expresses BCR-ABL1 due to the subclonal evolution of tumor heterogeneity developing drug resistance 3, including the subclonal acquisition of a BCR::ABL1 fusion in CML 4 and of that KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the upregulation of HOX genes plus concurrent mutations of ASXL1 and RUNX1 in AML5, as well as point mutations (T315I mutations) in the BCR-ABL1 fusion gene in CML6.