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

doi:10.1080/10428194.2018.1439167

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

Research output: Contribution to journal › Article › peer-review

15 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 language	English (US)
Pages (from-to)	2686-2691
Number of pages	6
Journal	Leukemia and Lymphoma
Volume	59
Issue number	11
DOIs	https://doi.org/10.1080/10428194.2018.1439167
State	Published - Nov 2 2018

Keywords

CLL
ibrutinib
lipoprotein lipase
metabolism

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1080/10428194.2018.1439167

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title = "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{\textquoteright} 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.",

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doi = "10.1080/10428194.2018.1439167",

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AU - Rozovski, Uri

AU - Harris, David M.

AU - Li, Ping

AU - Liu, Zhiming

AU - Jain, Preetesh

AU - Ferrajoli, Alessandra

AU - Burger, Jan

AU - Thompson, Phillip

AU - Jain, Nitin

AU - Wierda, William

AU - Keating, Michael J.

AU - Estrov, Zeev

PY - 2018/11/2

Y1 - 2018/11/2

N2 - 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.

AB - 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.

KW - CLL

KW - ibrutinib

KW - lipoprotein lipase

KW - metabolism

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JO - Leukemia and Lymphoma

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ER -

Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia

Abstract

Keywords

ASJC Scopus subject areas

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