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The traditional tumor target paradigm aims to treat hematological malignancies such as acute myeloid leukemia (AML) by focusing on the specificity and potency of therapies that kill cancer cells expressing a target. However, this paradigm is limited by the expression of tumor targets on healthy cells, resulting in on-target toxicity. On-target toxicity has led to the development failure of many targeted therapies and is often a key mechanism limiting therapeutic use or dose.