Epstein-Barr Virus-Driven B-Cell Transformation under Germinal Center Hypoxia Requires External Unsaturated Fatty Acids DOI

Larissa Havey,

Haixi You, John M. Asara

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Epstein-Barr virus (EBV) contributes to over 200,000 cancers annually, predominantly aggressive lymphomas originating from hypoxic germinal centers (< 1% O₂). However, conventional models fail recapitulate the physiologically relevant microenvironment which profoundly influences B-cell metabolic remodeling during transformation. Here, we establish an ex vivo model of EBV-driven transformation under O₂, demonstrating robust and super-enhancer activation oncogenic regulators, including MYC. Multi-omic analyses reveal distinct adaptations hypoxia. Unlike normoxic B-cells, rely on fatty acid desaturases oxidation mitigate lipotoxicity, hypoxically transformed B-cells suppress synthesis while upregulating glycerophospholipid metabolism lipid droplet formation buffer excess saturated lipids. Consequently, these cells exhibit heightened dependence external unsaturated acids support proliferation. Our findings provide first hypoxia, uncovering vulnerabilities that could inform targeted therapeutic strategies for EBV-associated malignancies.

Язык: Английский

Epstein-Barr Virus-Driven B-Cell Transformation under Germinal Center Hypoxia Requires External Unsaturated Fatty Acids DOI

Larissa Havey,

Haixi You, John M. Asara

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Epstein-Barr virus (EBV) contributes to over 200,000 cancers annually, predominantly aggressive lymphomas originating from hypoxic germinal centers (< 1% O₂). However, conventional models fail recapitulate the physiologically relevant microenvironment which profoundly influences B-cell metabolic remodeling during transformation. Here, we establish an ex vivo model of EBV-driven transformation under O₂, demonstrating robust and super-enhancer activation oncogenic regulators, including MYC. Multi-omic analyses reveal distinct adaptations hypoxia. Unlike normoxic B-cells, rely on fatty acid desaturases oxidation mitigate lipotoxicity, hypoxically transformed B-cells suppress synthesis while upregulating glycerophospholipid metabolism lipid droplet formation buffer excess saturated lipids. Consequently, these cells exhibit heightened dependence external unsaturated acids support proliferation. Our findings provide first hypoxia, uncovering vulnerabilities that could inform targeted therapeutic strategies for EBV-associated malignancies.

Язык: Английский

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