Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia

Uri Rozovski, David M. Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J. Keating, Zeev Estrov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)2686-2691
Number of pages6
JournalLeukemia and Lymphoma
Volume59
Issue number11
DOIs
StatePublished - 2 Nov 2018

Keywords

  • CLL
  • ibrutinib
  • lipoprotein lipase
  • metabolism

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