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Metabolic rewiring beyond Warburg in chronic lymphocytic leukemia: How much do we actually know?

期刊

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
卷 134, 期 -, 页码 65-70

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.critrevonc.2018.12.003

关键词

Primary CLL lymphocytes; BTK; ibrutinib; Central carbon metabolism rewiring; TP53; ATM

资金

  1. Leukemia and Lymphoma Society [360235]
  2. Rosenberg/Unger/Schwarzbard/Kallchman Hematology Research Award, Faculty of Medicine, McGill University

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Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia in the western world. CLL consists of the accumulation of malignant B-cells in the blood stream and homing tissues. Although treatable, this disease is not curable, and resistance or relapse is often present. In many cancers, the study of metabolic reprograming has uncovered novel targets that are already being exploited in the clinic. However, CLL metabolism is still poorly understood. The ability of CLL lymphocytes to adapt to diverse microenvironments is accompanied by modifications in cell metabolism, revealing the challenge of targeting the CLL lymphocytes present in all different compartments. Despite this, the study of CLL metabolism led to an ongoing clinical trial using glucose uptake and mitochondrial respiration inhibitors. In contrast, glutamine and fatty acid metabolism remain to be further exploited in CLL. Here, we summarize the present knowledge of CLL metabolism, as well as the metabolic influence of Myc, ATM and p53 on CLL lymphocytes.

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