Figure 1Lysis of Tumor Cells and the Release of DNA, Phosphate, Potassium, and Cytokines
The graduated cylinders shown in Panel A contain leukemic cells removed by leukapheresis from a patient with T-cell acute lymphoblastic leukemia and hyperleukocytosis (white-cell count, 365,000 per cubic millimeter). Each cylinder contains straw-colored clear plasma at the top, a thick layer of white leukemic cells in the middle, and a thin layer of red cells at the bottom. The highly cellular nature of Burkitt’s lymphoma is evident in Panel B (Burkitt’s lymphoma of the appendix, hematoxylin and eosin). Lysis of cancer cells (Panel C) releases DNA, phosphate, potassium, and cytokines. DNA released from the lysed cells is metabolized into adenosine and guanosine, both of which are converted into xanthine. Xanthine is then oxidized by xanthine oxidase, leading to the production of uric acid, which is excreted by the kidneys. When the accumulation of phosphate, potassium, xanthine, or uric acid is more rapid than excretion, the tumor lysis syndrome develops. Cytokines cause hypotension, inflammation, and acute kidney injury, which increase the risk for the tumor lysis syndrome. The bidirectional dashed line between acute kidney injury and tumor lysis syndrome indicates that acute kidney injury increases the risk of the tumor lysis syndrome by reducing the ability of the kidneys to excrete uric acid, xanthine, phosphate, and potassium. By the same token, development of the tumor lysis syndrome can cause acute kidney injury by renal precipitation of uric acid, xanthine, and calcium phosphate crystals and by crystal-independent mechanisms. Allopurinol inhibits xanthine oxidase (Panel D) and prevents the conversion of hypoxanthine and xanthine into uric acid but does not remove existing uric acid. In contrast, rasburicase removes uric acid by enzymatically degrading it into allantoin, a highly soluble product that has no known adverse effects on health.