Dysregulation of fatty acid synthesis and glycolysis in non-Hodgkin lymphoma

Abstract

The metabolic differences between B-NHL and primary human B cells are poorly understood. Among human B-cell non-Hodgkin lymphomas (B-NHL), primary effusion lymphoma (PEL) is a unique subset that is linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). We report that the metabolic profiles of primary B cells are significantly different from that of PEL. Compared with primary B cells, both aerobic glycolysis and fatty acid synthesis (FAS) are up-regulated in PEL and other types of nonviral B-NHL. We found that aerobic glycolysis and FAS occur in a PI3K-dependent manner and appear to be interdependent. PEL overexpress the fatty acid synthesizing enzyme, FASN, and both PEL and other B-NHL were much more sensitive to the FAS inhibitor, C75, than primary B cells. Our findings suggest that FASN may be a unique candidate for molecular targeted therapy against PEL and other B-NHL.

Kaposi's Sarcoma-Associated Herpesvirus-Positive Primary Effusion Lymphoma Tumor Formation in NOD/SCID Mice Is Inhibited by Neomycin and Neamine Blocking Angiogenin's Nuclear Translocation

“…Interestingly, the inhibition of AKT with miltefosine and perifosine, two alkylphospholipids, inhibited PEL cell growth, induced apoptosis in vitro, and delayed PEL tumor progression in vivo (72,73). Altogether, these studies indicated that ANG could also be protecting the PEL cells from apoptosis in part through the regulation of crucial antiapoptotic pathways, such as NF-B and AKT.…”

Metabolic Reprogramming of Macrophages

“…Fresh medium was added, and cells were grown for an additional 24 h. PBS-washed cells were detached by scraping and pelleted for analysis by Metabolon, Inc. (Durham, NC) as in Bhatt et al (23). Data are presented as relative measures of "scaled intensity" after normalization to protein and median scaling to 1.…”

Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids

“…We hypothesized that regulation of lipid metabolism could be an important component of BaP anticancer activity given that abnormally rapid lipogenesis is considered to be a hallmark of most cancers (15,16). Elevated lipogenesis in tumor cells is at least partly caused by high rates of fatty acid biosynthesis (15)(16)(17)(18), a phenomenon also observed in hematologic malignancies (19,20). Enzymes that synthesize saturated fatty acids [acetyl CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN)] and monounsaturated fatty acids [stearoyl CoA desaturase 1 (SCD1)] are often overexpressed in malignant cells, and selective inhibition of these enzymes exerts an anticancer effect in vitro (18,(20)(21)(22)(23)(24).…”