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 acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice.


METHODS
NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia was monitored throughout the development of disease by determination of absolute leukemic cell counts (LCC) in peripheral 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 first leukemic cells in peripheral blood, LCC increased exponentially. Leukemic cells showed specificity of homing to spleen and bone marrow, and LCC strongly correlated with the level of leukemic engraftment in these organs throughout disease progression, demonstrating that LCC are representative for overall leukemic burden. Cytogenetic analysis of leukemic cells recovered after six successive in vivo transfers revealed no major karyotypic changes as compared to primary cells, and selection of the dominant clones was observed. This selection process was reflected by an increase in the rate of leukemic progression as compared to the first inoculation, demonstrating the accuracy with which kinetics of leukemic progression can be studied by determination of LCC.


CONCLUSIONS
This model is suitable for detailed studies of kinetics and characteristics of ALL in vivo, and it may be useful for monitoring effects of novel therapeutic regimens.
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. b.a.nijmeijer@lumc.nl
B A
BA
Nijmeijer
P
P
Mollevanger
S L
SL
van Zelderen-Bhola
H C
HC
Kluin-Nelemans
R
R
Willemze
J H
JH
Falkenburg
D000328:Adult; D000818:Animals; D001752:Blast Crisis / Q000473:pathology; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure; D018450:Disease Progression; D005260:Female; D006085:Graft Survival; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D017254:Leukemic Infiltration; D008221:Lymphoid Tissue / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D009368:Neoplasm Transplantation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D014178:Translocation, Genetic; D014183:Transplantation, Heterologous