Inhibition of Wnt signaling in hematopoietic stem cells reduces their capacity to self-renew and regenerate the hematopoietic system.117 Dysregulated Wnt signaling is implicated in the malignant transformation and the maintenance of LSCs in AML and chronic myeloid leukemia (CML).118,119 In T-ALL, Giambra et al. observed activated Wnt signaling in a subpopulation of cells enriched for LSCs in NOTCH1-ΔE induced leukemia mouse model. Here, NOTCH1 is linked to acute lymphoblastic leukemia.