Cancer Signaling Pathways in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a complex and heterogeneous hematological malignancy characterized by abnormal proliferation and impaired differentiation of myeloid precursor cells. The pathogenesis of AML is strongly associated with dysregulation of multiple cancer signaling pathways that control cellular proliferation, survival, apoptosis, metabolism, and stem cell maintenance. Key signaling cascades implicated in AML include FLT3, PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, JAK/STAT, NF-κB, Wnt/β-catenin, Hedgehog, Notch, and p53 pathways. Aberrant activation or suppression of these pathways contributes to leukemogenesis, disease progression, therapeutic resistance, and relapse. FLT3 mutations represent one of the most common molecular abnormalities in AML and are closely linked with activation of downstream oncogenic signaling networks. Similarly, constitutive activation of PI3K/Akt/mTOR and MAPK pathways promotes leukemic cell growth and survival, while dysregulation of Wnt/β-catenin and Hedgehog pathways supports leukemic stem cell maintenance. In addition, alterations in JAK/STAT, NF-κB, and p53 signaling further contribute to AML pathophysiology and poor clinical outcomes. The extensive cross-talk among these pathways highlights the molecular complexity of AML and presents challenges for effective treatment. Understanding the mechanisms underlying signaling pathway dysregulation in AML remains essential for the development of targeted therapeutic strategies and improved patient management.