2007
DOI: 10.1038/sj.leu.2405058
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Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results in apoptosis of B-cell chronic lymphocytic leukemia cells

Abstract: Constitutively activated pathways contribute to apoptosis resistance in chronic lymphocytic leukemia (CLL). Little is known about the metabolism of lipids and function of lipases in CLL cells. Performing gene expression profiling including B-cell receptor (BCR) stimulation of CLL cells in comparison to healthy donor CD5 þ B cells, we found significant overexpression of lipases and phospholipases in CLL cells. In addition, we observed that the recently defined prognostic factor lipoprotein lipase (LPL) is induc… Show more

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Cited by 86 publications
(73 citation statements)
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“…Together with data from other groups, the present study underscores the importance of lipid metabolism for activated and malignant human B cells (84). Given that inhibitors of geranylgeranylation are still in the early phases of clinical development and that there are numerous statins that are already on the market, lipophilic statins such as simvastatin and atorvastatin appear to be ideal candidates for the rapid translation into clinical application.…”
Section: Discussionsupporting
confidence: 54%
“…Together with data from other groups, the present study underscores the importance of lipid metabolism for activated and malignant human B cells (84). Given that inhibitors of geranylgeranylation are still in the early phases of clinical development and that there are numerous statins that are already on the market, lipophilic statins such as simvastatin and atorvastatin appear to be ideal candidates for the rapid translation into clinical application.…”
Section: Discussionsupporting
confidence: 54%
“…Recently, we demonstrated BCR-induced expression of LPL as a prognostic and pathogenetic factor in CLL. 21 An unmutated status of the IgV H gene was shown to exhibit enhanced autoreactivity and was shown to be the most reliable predictor of prognosis in CLL. 22 Interestingly, we could show that IgV H -unmutated CLL cases exhibited significantly higher expression levels of TOSO.…”
Section: Discussionmentioning
confidence: 99%
“…Although the doses used here to exert the proapoptotic and antiproliferative actions of BEZ exceed this by 20-fold, experience of overdose in humans and rhesus monkeys indicates that 30 times the standard daily dose is tolerated without ill effect, for up to a year. 36 On a cautionary note, it has been demonstrated that elevated lipoprotein lipase is a poor risk factor in CLL, 37 that the lipoprotein lipase-inhibitor orlistat induces apoptosis of CLL cells in vitro 38 and that BEZ elevated lipoprotein lipase in hypertriglyceridemic patients during BEZ administration. 39 Medroxyprogesterone acetate has been used to treat breast and renal cell cancers.…”
Section: Discussionmentioning
confidence: 99%