مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
The Role of Lipid Metabolism in Leukemia: A Review of Lipid Biosynthesis and Signaling Mechanisms
The Role of Lipid Metabolism in Leukemia: A Review of Lipid Biosynthesis and Signaling Mechanisms
AmirHossein RahimBakhsh,1,*
1. Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Introduction: Lipid metabolism is a fundamental cellular process that plays a crucial role in maintaining cellular homeostasis by providing energy, building structural components of membranes, and generating bioactive signaling molecules. Growing evidence indicates that dysregulation of lipid metabolism contributes significantly to the pathophysiology of cancer, including hematological malignancies such as leukemia. Leukemia, a malignant blood disorder characterized by uncontrolled proliferation of abnormal hematopoietic cells, has been increasingly linked to alterations in lipid metabolic pathways. Disturbances in lipid metabolism, by altering lipid-dependent signaling pathways that regulate the cell cycle and programmed cell death (apoptosis), increase the survival and growth of leukemic cells. Certain lipids and their derivatives, including hormones and growth factors, act as signaling molecules essential for leukemic cell proliferation. Moreover, upregulation of lipid biosynthetic enzymes, enhanced intracellular lipid storage, and remodeling of membrane lipid composition further sustain disease progression. A deeper understanding of these mechanisms may help identify novel therapeutic targets and inform the development of more effective therapeutic strategies.
Methods: We conducted a comprehensive search of PubMed, Scopus, and Web of Science databases to investigate the role of lipid metabolism in leukemia, focusing on studies published between 2004 and 2024. The search strategy included the keywords “lipid metabolism,” “leukemia,” “lipid biosynthesis,” “cholesterol,” “phospholipids,” “triglycerides,” “mTOR pathway,” and “AMPK signaling.” Eligible studies were limited to original experimental research investigating lipid biosynthesis, lipid signaling, and their roles in the development and progression of leukemia. Studies that did not align with the inclusion criteria or were not published in peer-reviewed journals were excluded from this review.
Results: Findings indicate that key lipid biosynthesis enzymes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and PI3K are consistently upregulated in leukemic cells, increasing the supply of fatty acids, cholesterol, and phospholipids that drive rapid proliferation. Lipid droplet accumulation in leukemic blasts enhances survival under metabolic stress and is linked to poor prognosis in acute myeloid leukemia (AML). Disruptions in lipid-dependent signaling pathways, particularly mTOR and AMPK, promote leukemic growth and resistance to apoptosis, while alterations in membrane lipid composition, including elevated cholesterol and saturated fatty acids, strengthen cell rigidity and stress resistance. In addition, bioactive lipids such as sphingolipids and prostaglandins act as signaling molecules that regulate survival and proliferation, with sphingosine-1-phosphate supporting leukemic expansion and ceramide promoting apoptosis. Aberrant cholesterol metabolism, through de novo synthesis and increased LDL uptake, further contributes to chemotherapy resistance.
Conclusion: These findings show that dysregulated lipid metabolism plays a central role in leukemia pathogenesis by upregulating biosynthetic enzymes, reprogramming lipid-dependent signaling pathways, altering membrane lipid composition, and promoting lipid droplet accumulation. Bioactive lipids such as sphingolipids and prostaglandins further regulate survival and apoptosis, contributing to leukemic progression and therapy resistance. Together, these mechanisms highlight lipid metabolism as both a driver of disease and a promising therapeutic target. Future research should focus on translating these insights into clinical applications, using lipid-related pathways and biomarkers to improve diagnosis, prognosis, and treatment strategies in leukemia.