Fig. 2: Schematic representation of T-LGLL pathogenesis.

The first step of T-large granular lymphocytes (T-LGL) proliferation is related to a chronic viral or auto-antigen stimulation (1), leading to T-LGLs activation. Then a storm of pro-inflammatory cytokines and chemokines, particularly produced by monocytes, sustains and fosters T-LGL proliferation (2). A third event leads to a monoclonal expansion leading to resistance to the physiological mechanism of activation induced cell death (AICD), to dysregulation of pro- and anti-apoptotic genes expression, as well as to somatic mutations, such as STATs mutations (3). These events promote the survival and the maintenance of the neoplastic clone, leading to the establishment of T-LGLL. The figure has been created by BioRender.com.