The treatment of refractory/resistant and extramedullary disease inchildhood acute lymphoblastic leukemia (ALL) remains problema-tical. A better biological understanding of the factors involved inleukaemic cell growth, migration and survival should aid develop-ment of novel therapeutic approaches. Two independent genome-wide association studies have identified polymorphisms in theinterleukin-15 (IL-15) gene as predictors of 1) leukemia developmentand 2) resistance to initial therapy. In addition, IL-15 mRNA levelshave been shown to predict the likelihood of central nervous system(CNS) relapse in childhood ALL. IL-15 is a cytokine with autocrineand paracrine effects on T and B cell survival. It is also important forleukocyte migration and alters adhesion molecule expression. Thesecharacteristics support a putative role for IL-15 in leukaemic growth,survival and/or cell migration to sites such as the CNS but this is yetto be tested. In this study we aimed to investigate the biologicalimpact of IL-15 on pre-B ALL cells.We compared the gene and protein expression of IL-15 and itshetero-trimeric receptor (IL-15Ra, b and g) in pre-B ALL cell linesusing Taqman low density qPCR arrays and flow cytometry. Wefound variable levels of expression, with high levels of both IL-15 andits receptor seen in cell lines known to be capable of extramedullaryinfiltration. Transmigration assays failed to show any chemotaxistowards IL-15 in IL-15 receptor expressing cell lines. Using MTT, cellgrowth curves and Annexin V assays we showed that addition ofexogenous IL-15 enhanced the growth of cells in vitro whilstneutralization of the IL-15R significantly reduced their growth.Future studies will investigate the effects of IL-15 on response tochemotherapeutic agents.In summary, these results support a potential role for IL-15 inextramedullary disease and strengthen our hypothesis that IL-15 isinvolved in the growth/survival of ALL cell lines.
- lymphoblastic leukaemia cells
- lymphoblastic leukaemia