Chemosensitizing Effect of Fenretinide-Induced NF-κb Inhibition in AML Therapy

INTRODUCTION: Acute myeloid leukemia (AML) represents a genetically heterogeneous hematological malignancy and is among top 10 common cancers in China. Though most cases achieve complete remission with current therapy, relapses eventually occur and subsequent therapies fail to eliminate the leukemic cells again and sustain long-term remission. Acquired resistance might be the real instigator of treatment failure. Nuclear factor kappa B (NF-κB) signaling pathway activation, a hallmark of primary AML cells, especially of leukemic stem cells (LCSs) and in vitro cell lines, and associated with multi-layered roles in AML pathogenesis, i.e., pre-leukemia myelodysplastic syndrome (MDS), LSCs, drug response/toxicity, relapse, and leukemic maintenance. Thus, NF-κB might be an attractive strategy for better treatment response and survival but less toxicity in AML therapy.