TY - JOUR
T1 - Case Series:Acute Tumor Lysis Syndrome in Mutator Mice with Disseminated Lymphoblastic Lymphoma
AU - Treuting, Piper M.
AU - Albertson, Tina M.
AU - Preston, Bradley D.
N1 - Funding Information:
We thank Donovan Anderson, Cammy Mason, and Scott Paulson for technical assistance; Julie Randolph-Habecker for immunohistochemistry; Bobbie Schneider for electron microscopy assistance; Charles Frevert and Brian Johnson for fluorescence imaging; and Diana Lim for illustrations. This work was supported by the National Institutes of Health (R01 ES09927, R01 CA098243, R01 CA111582, and P01 CA77852 to B.D.P.; P01 AG01751 to B.D.P. and P.M.T.), the National Institute of Environmental Health Sciences–sponsored Center for Ecogenetics and Environmental Health (P30 ES07033), and the Comparative Mouse Genomics Center (U01 ES11045) at the University of Washington. T. M. A. was supported by a Young Investigators Award from Seattle Children’s Hospital.
PY - 2010/4
Y1 - 2010/4
N2 - Acute tumor lysis syndrome (ATLS) is characterized by severe metabolic abnormalities and organ dysfunction resulting from rapid destruction of neoplastic cells. Metabolic disturbances are thought to be the primary cause of clinical ATLS symptoms, which include renal dysfunction, seizures, and cardiac arrhythmias. The histopathologic lesions associated with organ dysfunction are largely unknown because of the low rate of mortality of ATLS in humans and the few cases of ATLS identified in laboratory animals. Here, we describe histologic, immunohistochemical, and electron microscopic analyses of thirty-one ATLS cases from a cohort of 499 mice that are prone to spontaneous lymphoblastic lymphoma owing to genetic defects in DNA replication fidelity. Seventy-three percent of our cohort died with lymphoblastic lymphoma, and 8% of affected mice died with diffuse microthromboemboli consistent with ATLS. Mice with ATLS had a high spontaneous mortality rate (>50%), a large tumor burden with disseminated disease, and evidence of leukemia. Blood vessels in the lung, kidney, and other organs were occluded by microthromboemboli composed of chromatin, cellular debris, fibrin, platelets, and entrapped erythrocytes and malignant cells. This case series suggests that ATLS can occur at high frequency in mice with disseminated lymphoblastic lymphoma and leads to a high rate of spontaneous death from microthromboemboli.
AB - Acute tumor lysis syndrome (ATLS) is characterized by severe metabolic abnormalities and organ dysfunction resulting from rapid destruction of neoplastic cells. Metabolic disturbances are thought to be the primary cause of clinical ATLS symptoms, which include renal dysfunction, seizures, and cardiac arrhythmias. The histopathologic lesions associated with organ dysfunction are largely unknown because of the low rate of mortality of ATLS in humans and the few cases of ATLS identified in laboratory animals. Here, we describe histologic, immunohistochemical, and electron microscopic analyses of thirty-one ATLS cases from a cohort of 499 mice that are prone to spontaneous lymphoblastic lymphoma owing to genetic defects in DNA replication fidelity. Seventy-three percent of our cohort died with lymphoblastic lymphoma, and 8% of affected mice died with diffuse microthromboemboli consistent with ATLS. Mice with ATLS had a high spontaneous mortality rate (>50%), a large tumor burden with disseminated disease, and evidence of leukemia. Blood vessels in the lung, kidney, and other organs were occluded by microthromboemboli composed of chromatin, cellular debris, fibrin, platelets, and entrapped erythrocytes and malignant cells. This case series suggests that ATLS can occur at high frequency in mice with disseminated lymphoblastic lymphoma and leads to a high rate of spontaneous death from microthromboemboli.
KW - DNA polymerase
KW - DNA replication
KW - acute tumor lysis syndrome
KW - lymphoblastic lymphoma
KW - mismatch repair
KW - mutator
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U2 - 10.1177/0192623310362249
DO - 10.1177/0192623310362249
M3 - Article
C2 - 20190201
AN - SCOPUS:77952523879
SN - 0192-6233
VL - 38
SP - 476
EP - 485
JO - Toxicologic Pathology
JF - Toxicologic Pathology
IS - 3
ER -