Following the Life History of Lymphocytes 
(The protein is an enzyme that can digest certain 
other proteins.) At the same time we had devel- 
oped several subclones from a clonal line of Abel- 
son leukemias, some that expressed Ag molecules 
(Ag*") and others that did not express them 
(Ag"^S) . The Ag''* and Ag"^^ lines were stable for 
those properties over tens of cell generations in 
the test tube. 
We wished to test if Ag*" cells might use their 
cell-surface protease to digest the surrounding 
tissues, invade adjacent blood vessels, and spread 
via the bloodstream to distant sites. Our experi- 
ments support this hypothesis. Ag*" subclones 
placed in the thigh muscle grew locally, invaded 
the bloodstream at our earliest observation inter- 
val (6 days), and killed 50 percent of the hosts in 
17 days. The same number of Ag"''^ subclones 
placed in the thigh muscle grew locally, but no 
cells could be found in the blood until 17 days, 
and the 50 percent death point came at 28 days. 
Thus, although the tumors grew locally at 
roughly equal rates, only the Ag*" cells invaded 
the bloodstream early and caused early deaths. 
Perhaps most significantly, the bloodstream 
leukemia derived from Ag"^^ cells now contained 
a significant fraction of Ag*'' cells — which did not 
occur when they grew in the test tube. That the 
early death of animals was due to the high inva- 
sive properties of Ag'" cells rather than some in- 
trinsic growth advantage they might possess was 
made clear when we showed that equal numbers 
of Ag''' and Ag"^^ cells injected directly into the 
bloodstream led to death of leukemic hosts at al- 
most the same time. 
We now need to know how reproducible this 
condition is and whether manipulation of the se- 
quence encoding the Ag will reveal how the en- 
zyme acts in malignant cells to promote their 
invasiveness and in normal bone marrow differ- 
entiating from hematopoietic stem cells to B lym- 
phocytes. And we need to determine whether 
there is a human homologue active in normal and 
neoplastic hematopoiesis. 
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