Monitoring of engraftment and progression of acute lymphoblastic leukemia in individual NOD/SCID mice

Objective. The aim of this study was to develop an animal model for human a cute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. Materials and Methods. NOD/SCID mice were inoculated intravenously with pri mary ALL. Progression of leukemia was monitored throughout the development of disease by determination of absolute leukemic cell counts (LCC) in perip heral blood. Results. LCC as low as 10(4) leukemic cells/mL blood could be detected. ALL cells from 5 of 5 patients engrafted, and after identification of the firs t leukemic cells in peripheral blood, LCC increased exponentially. Leukemic cells showed specificity of homing to spleen and bone marrow, and LCC stro ngly correlated with the level of leukemic engraftment in these organs thro ughout disease progression, demonstrating that LCC are representative for o verall leukemic burden. Cytogenetic analysis of leukemic cells recovered af ter six successive in vivo transfers revealed no major karyotypic changes a s compared to primary cells, and selection of the dominant clones was obser ved. This selection process was reflected by an increase in the rate of leu kemic progression as compared to the first inoculation, demonstrating the a ccuracy with which kinetics of leukemic progression can be studied by deter mination of LCC, Conclusions. This model is suitable for detailed studies of kinetics and ch aracteristics of ALL in vivo, and it may be useful for monitoring effects o f novel therapeutic regimens. (C) 2001 International Society for Experiment al Hematology. Published by Elsevier Science Inc.