Differential kinetics of engraftment and induction of CD10 on human pre-B leukemia cell lines in immune deficient scid mice.
The sensitivity of the scid mouse model was assessed by comparing the growth of two pre-B acute lymphoblastic leukemia (ALL) cell lines, A1 and G2, established from patients at relapse. When cell numbers varying from 10(4) to 10(7) were injected intravenously into scid mice, advanced growth and dissemination of leukemia was observed at 10-12 weeks with the G2 cells. Bone marrow, spleen and thymus contained high levels of human leukemic cells and infiltration into lung, kidney, liver, and brain was observed. Two of three mice grafted with only 100 cells showed high levels of infiltration at 15 weeks, suggesting that 100 G2 cells was near the limiting cell number that could produce disseminated leukemia. With the A1 line, a minimum of 10(5) cells was needed to obtain dissemination to liver, lung, brain, and kidney; a low level of spleen infiltration occurred and thymus invasion was not observed. In vitro, both lines showed a density dependent growth in clonogenic assays but the cloning efficiency of the A1 line was 10-fold higher than for G2 cells. These results indicate that G2 and A1 lines have a dissimilar aggressiveness in vivo which does not correlate with clonogenic assay in vitro. Neither G2 nor A1 lines, growing in vitro, expressed CD10/CALLA on their surface, despite low levels of antigen on the freshly obtained relapse samples. Although A1 cells remained CD10-negative in the scid mice, G2 cells showed detectable levels of CD10, particularly on those cells found in the thymus. Several subclones of the G2 line were derived from isolated colonies in vitro; they were found to be CD10- in vitro, but to become CD10+ when proliferating into scid mouse thymus, suggesting the induction of CD10 by the murine microenvironment.
Kamel-Reid
S
S
Department of Genetics, Hospital for Sick Children, Toronto, Canada.
Dick
J E
JE
Greaves
A
A
Murdoch
B
B
Doedens
M
M
Grunberger
T
T
Thorner
P
P
Freedman
M H
MH
Phillips
R A
RA
Letarte
M
M
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; D004273:DNA, Neoplasm / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation / Q000473:pathology; D015260:Neprilysin; D010641:Phenotype; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000473:pathology; D014410:Tumor Stem Cell Assay
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D016201:Receptors, Lymphocyte Homing; D015260:Neprilysin