LAUSR

Simple Summary AML is a highly heterogeneous hematological disease and is the second most common form of leukemia. Around 40% of AML patients display elevated nuclear NF-κB activity, providing a compelling rationale for targeting the NF-κB pathway in AML. Here we summarize the main drivers of the NF-κB pathway in AML pathogenesis as well as the conventional and novel therapeutic strategies targeting NF-κB to improve the survival of AML patients. Abstract Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy that relies on highly heterogeneous cytogenetic alterations. Although in the last few years new agents have been developed for AML treatment, the overall survival prospects for AML patients are still gloomy and new therapeutic options are still urgently needed. Constitutive NF-κB activation has been reported in around 40% of AML patients, where it sustains AML cell survival and chemoresistance. Given the central role of NF-κB in AML, targeting the NF-κB pathway represents an attractive strategy to treat AML. This review focuses on current knowledge of NF-κB’s roles in AML pathogenesis and summarizes the main therapeutic approaches used to treat NF-κB-driven AML.