TY - JOUR
T1 - Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia
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
N1 - Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
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
UR - http://www.scopus.com/inward/record.url?scp=85042233053&partnerID=8YFLogxK
U2 - 10.1080/10428194.2018.1439167
DO - 10.1080/10428194.2018.1439167
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C2 - 29465264
AN - SCOPUS:85042233053
SN - 1042-8194
VL - 59
SP - 2686
EP - 2691
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 11
ER -