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Acute lymphoblastic leukemia and non-Hodgkin's lymphoma of T lineage:
colony-forming cells retain growth factor (interleukin 2) dependence
I Touw, R Delwel, G van Zanen and B Lowenberg
The regulatory role of interleukin 2 (IL 2) in the proliferation of T acute
lymphoblastic leukemia (T-ALL) and T non-Hodgkin's lymphoma (T- NHL) cells
from six individual patients was analyzed in a colony culture system to
which pure recombinant IL 2, and the lectin phytohemagglutinin (PHA) or the
phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA), had been added.
The proliferative response was correlated with the inducibility of
receptors for IL 2 on the surface membrane of T-ALL and T-NHL cells by
incubation with TPA or PHA for 18 hours. Leukemic T cell colonies,
identified by immunophenotyping or cytogenetic analysis, appeared in vitro
following TPA and IL 2 stimulation in all six cases. Accordingly, receptors
for IL 2, initially absent from the cell surface, were found on high
proportions of the T-ALL and T-NHL cells after in vitro exposure to TPA. In
contrast, colony formation stimulated by PHA and the induction of IL 2
receptors by PHA were limited to the one case of T-NHL with the mature
thymocyte immunophenotype. The cells from the other patients, expressing
common or prothymocyte phenotypes, did not respond to PHA. No colonies were
formed in any of these cases when PHA or TPA was withheld from the IL
2-containing cultures. Although colony growth depended absolutely on
exogenous IL 2 in three cases (ALL), in the three other cases (one ALL, two
NHL) some colonies grew also when no IL 2 had been added to the cultures.
Upon further analysis of the cells of one of the latter patients, it was
found that the cells produced IL 2 and proliferated in response to this
endogenous IL 2. The results from this study indicate that the requirements
of endogenous v exogenous IL 2 for cell proliferation in T-ALL and T-NHL
and IL 2 receptor activation by PHA and TPA vary from patient to patient.
In addition, they support the notion that T-ALL and T-NHL cells have not
lost dependence on IL 2 and IL 2 receptor activation for in vitro growth.
Volume 68,
Issue 5,
pp. 1088-1094,
11/01/1986
Copyright © 1986 by The American Society of Hematology

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