Fatty acid synthase and adenosine monophosphate-activated protein kinase regulate cell survival and drug sensitivity in diffuse large B-cell lymphoma: Leuk Lymphoma

Grace K. Gifford, Andrew J. Gifford, Qian Chen, Yandong Shen, Sara Gabrielli, Anthony J. Gill, William S. Stevenson, Oliver Giles Best

Research output: Contribution to journalArticlepeer-review

Abstract

Fatty acid synthesis is crucial in supporting the survival and proliferation of multiple forms of cancer. The high metabolic demands of fatty acid synthesis are regulated by the AMP-activated kinase and activity of the fatty acid synthase enzyme. In this study, the roles of these enzymes in diffuse large B-cell lymphoma (DLBCL) were investigated by genetic knock-down and pharmacological activation of AMP-activated kinase by metformin, and selective inhibition of fatty acid synthase using the novel drug Fasnall. We observed distinct heterogeneity and adaptive plasticity of lipid metabolism in a panel of DLBCL cell lines and demonstrate the therapeutic potential of inhibiting fatty acid synthesis in a subset of DLBCL cells. The translational relevance of these in vitro data is supported by the strong correlation between AMP-activated protein kinase expression in primary DLBCL samples and disease relapse. Inhibition of fatty acid synthase with Fasnall may represent a therapeutic option for DLBCL that preferentially subverts to de novo fatty acid synthesis.
Original languageEnglish
Pages (from-to)1810-1822
Number of pages13
JournalLeukemia & lymphoma
Volume61
Issue number8
DOIs
Publication statusPublished - 2020
Externally publishedYes

Keywords

  • Adenosine Monophosphate Apoptosis Cell Line, Tumor Cell Survival Fatty Acid Synthases/genetics Humans *Lymphoma, Large B-Cell, Diffuse/drug therapy/genetics *Pharmaceutical Preparations Protein Kinases *Lymphoma and Non-Hodgkin disease *cell cycle and apoptosis changes *metabolism *pharmacotherapeutics
  • cell cycle and apoptosis changes
  • pharmacotherapeutics
  • metabolism
  • Lymphoma and Non-Hodgkin disease

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