ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia

Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352:804–15.

Article  CAS  PubMed  Google Scholar 

Scarfò L, Ferreri AJ, Ghia P. Chronic lymphocytic leukaemia. Crit Rev Oncol Hematol. 2016;104:169–82.

Article  PubMed  Google Scholar 

Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Perini GF, Feres CCP, Teixeira LLC, Hamerschlak N. BCL-2 Inhibition As Treatment For Chronic Lymphocytic Leukemia. Curr Treat Options Oncol. 2021;22:66.

Article  PubMed  Google Scholar 

De Novellis D, Cacace F, Caprioli V, Wierda WG, Mahadeo KM, Tambaro FP. The TKI era in chronic leukemias. Pharmaceutics. 2021;13:2201.

Article  PubMed  PubMed Central  Google Scholar 

Vander Heiden MG, DeBerardinis RJ. Understanding the intersections between metabolism and cancer biology. Cell. 2017;168:657–69.

Article  PubMed Central  Google Scholar 

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–33.

Article  Google Scholar 

Chen Z, Simon-Molas H, Cretenet G, Valle-Argos B, Smith LD, Forconi F, et al. Characterization of metabolic alterations of chronic lymphocytic leukemia in the lymph node microenvironment. Blood. 2022;140:630–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jitschin R, Hofmann AD, Bruns H, Giessl A, Bricks J, Berger J, et al. Mitochondrial metabolism contributes to oxidative stress and reveals therapeutic targets in chronic lymphocytic leukemia. Blood. 2014;123:2663–72.

Article  CAS  PubMed  Google Scholar 

Lu J, Böttcher M, Walther T, Mougiakakos D, Zenz T, Huber W. Energy metabolism is co-determined by genetic variants in chronic lymphocytic leukemia and influences drug sensitivity. Haematologica. 2019;104:1830–40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Galicia-Vázquez G, Smith S, Aloyz R. Del11q-positive CLL lymphocytes exhibit altered glutamine metabolism and differential response to GLS1 and glucose metabolism inhibition. Blood Cancer J. 2018;8:13.

Article  PubMed  PubMed Central  Google Scholar 

Werner A, Pieh D, Echchannaoui H, Rupp J, Rajalingam K, Theobald M, et al. Cationic amino acid transporter-1-mediated arginine uptake is essential for chronic lymphocytic leukemia cell proliferation and viability. Front Oncol. 2019;9:1268.

Article  PubMed  PubMed Central  Google Scholar 

Muggen AF, Pillai SY, Kil LP, van Zelm MC, van Dongen JJ, Hendriks RW, et al. Basal Ca(2+) signaling is particularly increased in mutated chronic lymphocytic leukemia. Leukemia. 2015;29:321–8.

Article  CAS  PubMed  Google Scholar 

Laubach K, Zhang J, Chen X. The p53 family: a role in lipid and iron metabolism. Front Cell Dev Biol. 2021;9:715974.

Article  PubMed  PubMed Central  Google Scholar 

Vangapandu HV, Havranek O, Ayres ML, Kaipparettu BA, Balakrishnan K, Wierda WG, et al. B-cell receptor signaling regulates metabolism in chronic lymphocytic leukemia. Mol Cancer Res. 2017;15:1692–703.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nie Y, Yun X, Zhang Y, Wang X. Targeting metabolic reprogramming in chronic lymphocytic leukemia. Exp Hematol Oncol. 2022;11:39.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Thurgood LA, Best OG, Rowland A, Lower KM, Brooks DA, Kuss BJ. Lipid uptake in chronic lymphocytic leukemia. Exp Hematol. 2022;106:58–67.

Article  CAS  PubMed  Google Scholar 

Friedman DR. Lipids and their effects in chronic lymphocytic leukemia. EBioMedicine. 2017;15:2–3.

Article  PubMed  Google Scholar 

Rozovski U, Grgurevic S, Bueso-Ramos C, Harris DM, Li P, Liu Z, et al. Aberrant LPL expression, driven by STAT3, mediates free fatty acid metabolism in CLL cells. Mol Cancer Res. 2015;13:944–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bilban M, Heintel D, Scharl T, Woelfel T, Auer MM, Porpaczy E, et al. Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression. Leukemia. 2006;20:1080–8.

Article  CAS  PubMed  Google Scholar 

Galicia-Vázquez G, Aloyz R. Ibrutinib resistance is reduced by an inhibitor of fatty acid oxidation in primary CLL lymphocytes. Front Oncol. 2018;8:411.

Article  PubMed  PubMed Central  Google Scholar 

Rombout A, Verhasselt B, Philippé J. Lipoprotein lipase in chronic lymphocytic leukemia: function and prognostic implications. Eur J Haematol. 2016;97:409–15.

Article  CAS  PubMed  Google Scholar 

Oppezzo P, Vasconcelos Y, Settegrana C, Jeannel D, Vuillier F, Legarff-Tavernier M, et al. The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia. Blood. 2005;106:650–7.

Article  CAS  PubMed  Google Scholar 

Liu PP, Liu J, Jiang WQ, Carew JS, Ogasawara MA, Pelicano H, et al. Elimination of chronic lymphocytic leukemia cells in stromal microenvironment by targeting CPT with an antiangina drug perhexiline. Oncogene. 2016;35:5663–73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

McCaw L, Shi Y, Wang G, Li YJ, Spaner DE. Low density lipoproteins amplify cytokine-signaling in chronic lymphocytic leukemia cells. EBioMedicine. 2017;15:24–35.

Article  PubMed  Google Scholar 

Talley JT, Mohiuddin SS. Biochemistry, fatty acid oxidation. StatPearls. © 2023, StatPearls Publishing LLC. Treasure Island FL, 2023.

Houten SM, Wanders RJA, Ranea-Robles P. Metabolic interactions between peroxisomes and mitochondria with a special focus on acylcarnitine metabolism. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165720.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Houten SM, Violante S, Ventura FV, Wanders RJ. The biochemistry and physiology of mitochondrial fatty acid β-oxidation and its genetic disorders. Annu Rev Physiol. 2016;78:23–44.

Article  CAS  PubMed  Google Scholar 

Ding L, Sun W, Balaz M, He A, Klug M, Wieland S, et al. Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis. Nat Metab. 2021;3:1648–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Violante S, Achetib N, van Roermund CWT, Hagen J, Dodatko T, Vaz FM, et al. Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4. FASEB J. 2019;33:4355–64.

Article  CAS  PubMed  Google Scholar 

Poirier Y, Antonenkov VD, Glumoff T, Hiltunen JK. Peroxisomal beta-oxidation-a metabolic pathway with multiple functions. Biochim Biophys Acta. 2006;1763:1413–26.

Article  CAS  PubMed  Google Scholar 

Pallasch CP, Schwamb J, Königs S, Schulz A, Debey S, Kofler D, et al. Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results in apoptosis of B-cell chronic lymphocytic leukemia cells. Leukemia. 2008;22:585–92.

Article  CAS  PubMed  Google Scholar 

Zheng FM, Chen WB, Qin T, Lv LN, Feng B, Lu YL, et al. ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells. BMB Rep. 2019;52:566–71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shen S, Faouzi S, Souquere S, Roy S, Routier E, Libenciuc C, et al. Melanoma persister cells are tolerant to BRAF/MEK inhibitors via ACOX1-mediated fatty acid oxidation. Cell Rep. 2020;33:108421.

Article  CAS  PubMed  Google Scholar 

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131:2745–60.

Article  CAS  PubMed  Google Scholar 

Cosson A, Chapiro E, Bougacha N, Lambert J, Herbi L, Cung HA, et al. Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1. Leukemia. 2017;31:1625–29.

Article  CAS  PubMed  Google Scholar 

Hertlein E, Beckwith KA, Lozanski G, Chen TL, Towns WH, Johnson AJ, et al. Characterization of a new chronic lymphocytic leukemia cell line for mechanistic in vitro and in vivo studies relevant to disease. PLoS One. 2013;8:e76607.

Article 

Comments (0)

No login
gif