Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia

Abstract

Unlike normal B-cells, and similar to fat cells, chronic lymphocytic leukemia (CLL) cells aberrantly express lipoprotein lipase (LPL), which contributes to free fatty acids (FFAs) metabolism. Here we show that, in CLL cells, the B-cell receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and inhibited FFA metabolism in vitro. Likewise, in CLL cells from ibrutinib-treated patients, FFA metabolism was reduced and eventually stopped. Because ibrutinib disrupts CLL cells’ ability to use FFAs for energy production, and because various BCR-dependent cellular functions rely on a continuous supply of chemical energy, ibrutinib interrupts several pathways imperative for cellular function in CLL cells.

Keywords:

• CLL
• ibrutinib
• metabolism
• lipoprotein lipase

Acknowledgements

We thank Laura Russel for editing our manuscript

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1439167.

Additional information

Funding

This study was supported by grants from the CLL Global Research Foundation and the Cancer Center Support Grant from the NIH/NCI, [P30 CA016672] and by the generous philanthropic contributions to The University of Texas MD Anderson CLL Moon Shots Program.