An investigation into the role of interleukin-15 on the growth and survival of pre-B acute lymphoblastic leukaemia cell lines

The treatment of refractory/resistant and extramedullary disease in
childhood acute lymphoblastic leukemia (ALL) remains problema-
tical. A better biological understanding of the factors involved in
leukaemic cell growth, migration and survival should aid develop-
ment of novel therapeutic approaches. Two independent genome-
wide association studies have identified polymorphisms in the
interleukin-15 (IL-15) gene as predictors of 1) leukemia development
and 2) resistance to initial therapy. In addition, IL-15 mRNA levels
have been shown to predict the likelihood of central nervous system
(CNS) relapse in childhood ALL. IL-15 is a cytokine with autocrine
and paracrine effects on T and B cell survival. It is also important for
leukocyte migration and alters adhesion molecule expression. These
characteristics support a putative role for IL-15 in leukaemic growth,
survival and/or cell migration to sites such as the CNS but this is yet
to be tested. In this study we aimed to investigate the biological
impact of IL-15 on pre-B ALL cells.
We compared the gene and protein expression of IL-15 and its
hetero-trimeric receptor (IL-15Ra, b and g) in pre-B ALL cell lines
using Taqman low density qPCR arrays and flow cytometry. We
found variable levels of expression, with high levels of both IL-15 and
its receptor seen in cell lines known to be capable of extramedullary
infiltration. Transmigration assays failed to show any chemotaxis
towards IL-15 in IL-15 receptor expressing cell lines. Using MTT, cell
growth curves and Annexin V assays we showed that addition of
exogenous IL-15 enhanced the growth of cells in vitro whilst
neutralization of the IL-15R significantly reduced their growth.
Future studies will investigate the effects of IL-15 on response to
chemotherapeutic agents.
In summary, these results support a potential role for IL-15 in
extramedullary disease and strengthen our hypothesis that IL-15 is
involved in the growth/survival of ALL cell lines.