Here we show that a knock-in reporter for the stem cell gene Musashi 2 (Msi2)18–20 can serve as a platform to define functional heterogeneity in hematological malignancies, and effectively identify LSCs in both blast crisis chronic myeloid leukemia (bcCML) and de novo AML. Here, MSI2 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.