Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016;57(4):758-65.
doi: 10.3109/10428194.2015.1106533. Epub 2015 Dec 8.

Metabolism pathways in chronic lymphocytic leukemia

Uri Rozovski  1   2 , Inbal Hazan-Halevy  3 , Merav Barzilai  2   4 , Michael J Keating  5 , Zeev Estrov  5
Affiliations
Review

Metabolism pathways in chronic lymphocytic leukemia

Uri Rozovski et al. Leuk Lymphoma. 2016.

Abstract

Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

Keywords: CLL; STAT3; lipoprotein lipase; metabolism; oxidative phosphorylation.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Model of lipid metabolism in CLL cells
A. In CLL cells signal transducer and activator of transcription (STAT)-3 is constitutively phosphorylated on serine 727 residues. Phosphorylated STAT3 forms dimers, shuttles to the nucleus, binds to DNA and activates STAT3-target genes. B. Because lipoprotein lipase (LPL) is a STAT3-target gene, LPL is aberrantly expressed in CLL cells. LPL is found in the cytosol and cell membrane of CLL cells and mediates cellular uptake of lipoproteins. C. Unlike in normal B lymphocytes, in CLL cells lipid vacuoles are scattered in the cytoplasm. D. LPL hydrolyzes triglycerides stored in lipid vacuoles into free fatty acids (FFAs). E. FFAs bind to and prompt proliferator-activated receptor (PPAR)-α shuttle into the nucleus. PPARα activates genes oxidative phosphorylation genes. F. PPARα-target gene proteins enter the mitochondria and induce oxidative phosphorylation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hammoudi N, Ahmed KB, Garcia-Prieto C, Huang P. Metabolic alterations in cancer cells and therapeutic implications. Chin J Cancer. 2011;30:508–525. - PMC - PubMed
    1. Bentley DP, Pepper CJ. The apoptotic pathway: a target for therapy in chronic lymphocytic leukemia. Hematol Oncol. 2000;18:87–98. - PubMed
    1. Dameshek W. Chronic lymphocytic leukemia--an accumulative disease of immunolgically incompetent lymphocytes. Blood. 1967;29(Suppl):566–584. - PubMed
    1. Kitada S, Pedersen IM, Schimmer AD, Reed JC. Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene. 2002;21:3459–3474. - PubMed
    1. Bueso-Ramos CE, Ferrajoli A, Medeiros LJ, Keating MJ, Estrov Z. Aberrant morphology, proliferation, and apoptosis of B-cell chronic lymphocytic leukemia cells. Hematology. 2004;9:279–286. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources