The Oncogenic Role of Mucin 1 (MUC1) and Its Therapeutic Potential in Acute Myeloid Leukemia

Abstract

Mucin 1 (MUC1), a transmembrane glycoprotein with critical roles in cell signaling and immune regulation, has been increasingly recognized as a key player in the pathogenesis of Acute Myeloid Leukemia (AML). Aberrant overexpression of MUC1 on leukemic blasts contributes to disease progression by promoting oncogenic signaling, enhancing resistance to apoptosis, and fostering immune evasion. Its hypoglycosylated form, predominantly observed in AML, disrupts normal cell-cell interactions, facilitates leukemic cell adhesion to the bone marrow niche, and contributes to chemoresistance. This review highlights the multifaceted role of MUC1 in AML pathophysiology, focusing on its involvement in the activation of critical pathways such as PI3K/Akt, NF-κB, and β-catenin, which promote leukemic cell survival, proliferation, and therapeutic resistance. Clinically, high MUC1 expression is correlated with adverse outcomes, including disease aggressiveness, relapse risk, and reduced survival, making it a promising biomarker for risk stratification. Emerging therapeutic strategies targeting MUC1 include monoclonal antibodies, peptide-based vaccines, small molecule inhibitors, and antibody-drug conjugates, many of which have demonstrated preclinical efficacy and are progressing to clinical evaluation. Novel immunotherapeutic approaches, such as MUC1-targeted chimeric antigen receptor (CAR) T-cell therapies, offer exciting potential to overcome chemoresistance and improve patient outcomes.

By synthesizing the latest research, this review underscores the clinical significance of MUC1 in AML and the transformative potential of MUC1-targeted therapies. Further investigation into the molecular mechanisms underlying MUC1’s oncogenic functions and the optimization of therapeutic strategies will be crucial for translating these insights into effective treatments for AML, ultimately improving survival and quality of life for affected patients.