Does IL-15 have a causative role in large granular lymphocyte leukemia?

Evaluation of: Mishra A, Liu S, Sams GH et al. Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. Cancer Cell 22(5), 645-655 (2012). There is increasing evidence identifying a link between inflammation and cancer. A potent proinflammatory cytokine, IL-15, stimulates the proliferation and maintenance of both NK and T cells, and it is therefore likely that it may play a prominent role in certain hematologic malignancies. Previous studies have demonstrated that IL-15 overexpression can initiate leukemic transformation in murine models and that both NK- and T-cell malignancies can develop; the mechanism is explored in this article. The authors illustrate that IL-15 can cause chromosomal instability and DNA hypermethylation in large granular lymphocytes. These aberrations led to an aggressive acute large granular lymphocyte leukemia. Through studying the affected pathways, the authors were able to identify potential therapeutic targets and induce remission in a murine model.