Abstract
Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of cytotoxic T/natural killer cells due to constitutive pro-survival signaling. In recent years, it has become clear that cytokines and their receptors are aberrantly expressed in LGLL cells. The exact initiation process of LGLL is unknown, although several cytokine-driven mechanisms have emerged. Elevated levels of several cytokines, including interleukin-15 (IL-15) and platelet-derived growth factor (PDGF), have been described in LGLL patients. Evidence from humans and animal models has shown that cytokines may also contribute to the co-occurrence of a wide range of autoimmune diseases seen in patients with LGLL. The goal of this review is to provide a comprehensive analysis of the link between cytokines and pro-survival signaling in LGLL and to discuss the various strategies and research approaches that are being utilized to study this link. This review will also highlight the importance of cytokine-targeted therapeutics in the treatment of LGLL.
Highlights
Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of effector cytotoxic T cells or natural killer (NK) cells
Sometimes included in the LGLL family, aggressive NK-cell leukemia (ANKL) is a distinct neoplasm of NK cells that is nearly always associated with Epstein–Barr virus (EBV) infection and has a very poor prognosis [2]
Studies examining the biology of LGLL have identified several altered growth factors signaling pathways in these leukemic cells, which induce molecular aberrancies believed to play a role in the development of LGLL and in its clinical and laboratory manifestations
Summary
Colleen Isabelle 1, Amy Boles 1, Nitin Chakravarti 1, Pierluigi Porcu 1, Jonathan Brammer 2 and Anjali Mishra 1,3*. Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disorder of older adults characterized by the clonal expansion of cytotoxic T/natural killer cells due to constitutive pro-survival signaling. It has become clear that cytokines and their receptors are aberrantly expressed in LGLL cells. Elevated levels of several cytokines, including interleukin-15 (IL-15) and platelet-derived growth factor (PDGF), have been described in LGLL patients. Evidence from humans and animal models has shown that cytokines may contribute to the co-occurrence of a wide range of autoimmune diseases seen in patients with LGLL. The goal of this review is to provide a comprehensive analysis of the link between cytokines and pro-survival signaling in LGLL and to discuss the various strategies and research approaches that are being utilized to study this link. This review will highlight the importance of cytokine-targeted therapeutics in the treatment of LGLL
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