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Figure 1. Intracellular signaling pathways dysregulated in AML LSCs, including agents recently used in clinical trials inhibiting pathway activity. (A) JAK/STAT signaling pathway. Therapeutic agents either target elevated JAK1/2 levels or constitutively active STAT3. (B) NF-κB signaling pathway. Therapeutic agents recently used in clinical trials directly inhibit the constitutively activated NF-κB. (C) Wnt/β-catenin signaling pathway. Therapeutic targets prevent constitutive activation by inhibiting the interaction between β-catenin and CBP or TCF. (D) Hh signaling pathway. Small molecule inhibitors target Smoothened (Smo), decreasing pathway activation. (E) Notch signaling pathway. There are currently no clinical trials inhibiting or activating the Notch pathway as a treatment in AML patients. Created with BioRender.com. AML: Acute myeloid leukemia; LSCs: leukemic stem cells; JAK/STAT: Janus kinase/signal transducer and activator of transcription; NF-κB: nuclear factor-kappa B; CBP: CREB-binding protein; TCF: T-cell factor; Hh: Hedgehog.